Dead Cells is described as a "roguevania", a combination of procedurally-generated roguelike games and action-exploration-based Metroidvania games. The player controls a mass of cells that at the start of each game, occupy and control the body of a deceased prisoner. The player collects weapon, armor, abilities, power-ups, and gold as they explore a set of dungeons and fighting the creatures that live within them. Should the controlled warrior's health fall to zero, the game is over, and the player must start again, losing all items and wealth acquired, with the dungeons having become re-generated again. Each level is procedurally generated by merging of predesigned sections in a random configuration along with random placement of enemies and items.
Permanent upgrades that affect future play-throughs can be obtained in a manner similar to the Souls series. Some enemies will drop cells when defeated. If the player can reach the end of a dungeon section, they can spend all collected cells towards power-ups that either affect how the player starts the game in the future, or adds items that can be found or bought in later runs. If the player fails to make it to the end of a dungeon section, they lose all collected cells.