The player's character is a member of a special law enforcement task force who is trapped in a mansion populated by dangerous mutated creatures. The objective of the game is to uncover the mystery of the mansion and ultimately escape alive. The game's graphics consist of real-time 3D polygonal characters and objects, superimposed over pre-rendered backdrops with fixed camera angles. The player controls the character by pushing the D-pad or analog stick left or right to rotate the character and then move the character forward or backwards by pushing the D-pad up or down (tank controls).

Players choose between two characters, Chris Redfield or Jill Valentine, each with their own unique differential abilities. Jill has more firepower and possesses a lock-pick that enables her to access areas and items easily, as well as an inventory large enough to hold up to eight items, while Chris has limited firepower but is more durable in terms of taking damage from enemies, and a smaller inventory that can hold only six items.

To fulfill the game's objective, the player uncovers various documents that provide exposition about the game's narrative, as well as clues that help them solve various puzzles within the mansion. Key items are also available that give the player access to other items or new areas. The player can arm their character with weapons to defend themselves from enemies, although the ammunition available for each firearm is limited and the player must learn to conserve the ammunition they have for situations where they will really need it. To restore the character's health, the player uses first-aid sprays or three types of healing herbs that can be mixed together in different combinations for different healing effects. The carrying capacity of the player is limited depending on the character and items that the player does not wish to carry at the moment can be stored into an item box to be retrieved for later use. To save their progress, the player must pick up an ink ribbon and use it on any of the typewriters scattered through key locations in the game. However, the supply of ink ribbons the player can acquire is limited, much like the player's ammunition and healing supplies. Players will encounter and fight various infected creatures such as flesh-eating zombies and zombie dogs, giant spiders, sharks, and other monsters. The player character is assisted by another character (Rebecca Chambers or Barry Burton) throughout the game.

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