According to the game's planner Hideki Kamiya in an interview published in the June 1998 issue of The PlayStation (JP) magazine, the pin-up poster in the laboratory originally featured a picture of Chun-Li from the Street Fighter series, but she was ultimately replaced with a different woman due to Kamiya thinking her appearance clashed too much with the world of Resident Evil.

In a 2020 interview conducted by the YouTube channel Archipel with series creator Shinji Mikami, he stated that the idea for when the first Hunter makes his appearance to kill the player came from the film The Texas Chainsaw Massacre:

Before its release, a free one-shot comic book produced by Marvel Comics detailing the events just before the start of the game was used to promote it in America. The cover art for the comic, drawn by Bill Sienkiewicz, was also used as the game's final cover art in North America. The person on the cover and initial protagonist of the comic is S.T.A.R.S. Bravo team member Richard Aiken.

In the DS version, Resident Evil: Deadly Silence, at the grave beneath the second Yawn battle, there's a new angle of the tombstone that reads 'LISA TREVOR'. This references the mutant girl of the same name who first appeared in the RE remake Resident Evil (2002).

The original Japanese version of the game contains an alternative credits scene where it shows the characters getting killed by enemies. To unlock it, the player must finish the game a second time (from a cleared save) and get a good ending.

The DS version's Multicard Play is the first time in the series nearly all canon S.T.A.R.S. members are playable and is also the only way to see Kenneth Sullivan, Forest Speyer, and Richard Aiken without any damage done to them in-game. The only missing S.T.A.R.S. members are Brad Vickers, Edward Dewey, and Joseph Frost, most likely because they never had actual character models in the game.

The international version of this game is more difficult than the original Japanese version. Some of the changes include having the auto-aiming function disabled and reducing the number of saves per ink ribbon from 6 to 3.

The change in difficulty was apparently done to give players less of a chance at beating the game on rental, so they'd have to buy it for themselves instead. Since renting video games in Japan is illegal, there was no need for the developers to increase the difficulty in the original Japanese version.

In the DS, both Japanese versions of the PlayStation and Saturn release, and some PC versions, the cutscene after encountering the first zombie includes a scene where Kenneth's head falls to the floor and rollls towards the camera. The head scene was removed from the other versions, even though his head is still detached from his body.

In later games containing the same scene, such as Resident Evil (2002) and Resident Evil: The Umbrella Chronicles, Kenneth's head remains attached to his body.

There are 3 different versions of the intro sequence for the game.

In the Japanese PlayStation version the intro is done in black and white with uncensored violence, in the French/German PlayStation Director's Cut, along with certain PC versions, it's the same as the Japanese version but in colour.
In the French/German PlayStation Director's Cut, Japanese version and some PC versions, Chris Redfield is smoking a cigarette during the cast section, but it was censored in the other versions.

Along with this, the Japanese version on PlayStation and certain PC versions, Chris Redfield's bad ending shows him smoking a cigarette in the helicopter, but it was censored in the other versions.

A newspaper, which shows a dead body is censored from the Japanese version. The Japanese Sega Saturn version however is left uncensored.

Hideki Kamiya admitted that he got "Joseph Frost's" first name from a Shonen Jump manga character named "Joseph Joestar" from JoJo's Bizarre Adventure.

Jill's first encounter with a zombie is when she finds one eating Kenneth Sullivan's corpse, near the beginning of the game. However, the scene will play out differently if the player returns to the lobby before encountering the zombie. The first time they leave the dining room, Wesker will tell Jill to go back. The second time, Barry will stop Jill from leaving, and then the zombie will burst into the room. If the player then visits the room with Kenneth's body, his legs will also be missing. This alternate scene is present in the director's cut but not in the 2002 remake.

During the opening cutscene in some versions of the game, the newspaper clipping misspells bizarre as "bizzar."

The Saturn version of the game also added a second Tyrant. After the player's first victory over the Tyrant that Wesker unleashes, when attempting to leave, another Tyrant will burst out of its stasis container.

A zombified Albert Wesker can be found in the Battle Game minigame, exclusive to the Saturn port. He is far more durable than other zombie enemies found in the game.

The Barry Lives ending had a major change to it. Spoiler:In the original, Wesker was decapitated in the power room by an unknown creature and his body was laying next to the control panel. In the remake, it was implied that he got away, as his body was missing.

A port of Resident Evil was planned for the GameBoy Color but was cancelled due to hardware limitations. The game was supposed to have new enemies and a new save feature. ROMs of the game have since been released online after a collector got their hands on an unfinished version of the game following a $2000 dollar fundraiser in order for him to do so.

Resident Evil was supposed to be multiplayer from the very beginning but that option was dropped due to hardware limitations.

In the Sega Saturn version of Resident Evil, the Hunter Alpha's of the original game were replaced by a variant called Tick, which was a somewhat insectoid looking Hunter with its sickle arms and antennae.

The cast to the original Resident Evil was supposed to compose of Jill and Chris but also two characters called Dewey (the team's african-american medic) and Geltzer (the team's huge radio operative). Dewey was planned as a comic relief and the name was later used for the STARS pilot.

Resident Evil was actually born from a project to create a successor to Capcom's Famicom game Sweet Home, which in turn was based on a movie of the same name.

Resident Evil's original Japanese name, Biohazard, was changed because trademarking "Biohazard" would have been too difficult, mostly due to a DOS game and a band of the same name. The name "Resident Evil" came from a naming contest held within the company.