In Room 209 of Blue Creek Apartments, there is a pre-determined once-per-playthrough chance of hearing a whisper after walking into the room. For years, it was unknown what this whisper was saying with fans who analyzed the audio clip speculating that it had to do with Spoiler:James reflecting on killing his wife Mary and leaving her body in his car at the beginning of the game, while one of the game's English localizers Jeremy Blaustein believed that it was a clip of one of the English voice actors practicing their lines in the sound booth, and was mistakenly added in by the Japanese developers who would not have known what it meant otherwise as it was unscripted. However, it was discovered in 2015 that the whisper was actually a snippet of a pre-existing stock sound effect of a man whispering gibberish.

When Eddie Dombrowski is shown during the Dog Ending credits Mira starts growling. This is most likely in reference to Eddie having killed a dog before, it's speculated that Mira could even be the dog Eddie killed.

Masahiro Ito, who designed the monsters for the game, said that he was inspired to create the Lying Figure when he saw a coworker walking toward him from a distance. The coworker was wearing a sweatshirt with a hood and had his hands in his pockets. He was listening to his Walkman and was walking in a "cool way."

Masahiro Ito's initial concept for the monster that would become Pyramid Head did not include the iconic helmet. The helmet was added to suggest pain.

There is persistent butterfly and moth symbolism surrounding Maria, who has a butterfly tattoo on her abdomen. Spoiler:Butterflies are seen as a symbol of rebirth in some cultures. Since she is supposed to be the reborn image of Mary, she could be seen as a butterfly. Likewise, moths are seen as a symbol of death, and Maria transforms into a swarm of black moths for the final boss. This parallels how James killed Mary.

Guy Cihi, who played James Sunderland, was only present at the auditions because he was escorting his daughter there. After reading a script in the break room, he asked if he could read for the part of James.

There is a hidden ending which reveals that a Shiba Inu dog had been controlling all of the events in the game, followed by the credits, accompanied with circus music and random pictures.