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Anime and Manga
- The Las Plagas Parasite is basically the same as the ones from Parasyte, right down to more mature hosts having blades come out of their heads when they split open from their hosts.
Film and TV
- The deadly Laser Hallway is taken straight from a similar scene in Resident Evil (2002).
- One of Leon's unlockable bonus weapons is called Matilda.
- This is also a shout-out to Resident Evil 2 as the main gun itself is the VP70 handgun Leon used in that game. You could find the parts to upgrade Leon's handgun to the Matilda, and Hunk had one listed as the Matilda in his inventory in "The 4th Survivor" subplot.
- Another reference to the film: the hardest difficulty setting is "Professional".
- The movie being referenced is Leon aka The Professional. The main characters of that film are named Leon and Mathilda.
- The Broken Butterfly's description mentions it will "make anyone's day." The Merchant also notes that the Broken Butterfy is "not just about shooting, it's about reloading. You'll know what I'm talking about."
- Ada's pose for "Separate Ways" mirrors the film poster for Nikita◊
- In Chapter 3-1, after defeating the first Garrador and turning off the flame barrier, three whiteheads in red robes greet Leon when he moves up the stairs. The first whitehead points at Leon and shouts, then runs back the way he came. He ends up standing in a corner facing the wall, like Mike at the end of The Blair Witch Project.
- Sometimes the zealots chant, "Cerebros, cerebros, cerebros" (spanish for "Brains, brains, brains"), a shoutout to 1985's The Return of the Living Dead.
- Luis' manner of death, impaled in the chest by surprise, from behind, by an previously unseen enemy, is a shoutout to Bishop's (non-fatal) evisceration in Aliens. Foreshadowed when Luis had earlier quoted Aliens in the cabin scene: "It's game time."
- Several of the story elements are taken straight off 24.
- The Dragon is named Ramon Salazar, after The Dragon in season three.
- The other Dragon is Jack Krauser, a slight change from Jack Bauer.
- Both the game and season three are centered on bioweapons and Spanish terrorists.
- Ada is working with the Big Bad and intends to double cross him much like Nina.
- The entire cabin scene is modeled off the central scenario in Night of the Living Dead (1968).
- Dr. Salvador and the "Bella Sisters" reference The Texas Chainsaw Massacre 1974 with their equipment and head-gear:
- Both sets of characters wield their chainsaws with iconic precision.
- The faces of both sets of characters cannot be seen due to an eye-slotted potato bag for the former and head bandages for the latter, referencing Leatherface.
- Dr. Salvador actually looks like Jason Vorhees did in Friday the 13th Part 2 with the overalls and sack instead of his iconic hockey mask.
- As pointed out by Jonathan Ferguson in a Gamespot video, the oversized laser sight on the Killer 7 handgun makes it look a lot like the ".45 longslide" that the T-800 uses in The Terminator.
- The Colmillos are straight up the Thing-dog from The Thing (1982).
- Help the trapped dog early on and he'll come back to help Leon in the first El Gigante fight. The dog is none other than Hewie from Haunting Ground. Also, the situation and result are a reference to the ancient Roman fable Androcles and the Lion.
- In Chapter Five of Separate Ways, the prompt for Ada's grappling hook changes to "Hook Shot."
- One of the weapons is not only titled killer7, but it also resembles KAEDE's gun from said game. Shinji Mikami both produced and helped Suda write killer7, and it was one of the other games in the "Capcom 5" set of (what were supposed to be) Gamecube-exclusives. Additionally, the way Leon rests the handcannon on his shoulder with the barrel behind his neck is identical to how Dan Smith carries his gun in killer7.
- After the above-mentioned laser hallway, there's what looks like a throne room with an elevator behind it. Sitting down on the throne makes Leon and the camera take a similar pose to Count Dracula.
- In the second area after reaching the Castle, Leon and Ashley are attacked by cannon fire. The first shot destroys a Dread Gazebo.
- Krauser's wearing a raspberry beret.
- Instead of a goose that lays golden eggs, the game has chickens that sometimes lay golden eggs.