The gameplay in Run Like Hell is most similar to that of the later titles in the Resident Evil series, with the player controlling a character from a third-person perspective. Enemies can be locked onto when firing and while reloading weapons is still required, most of the weapons have infinite ammo. The game also features a number of chase sequences, in which the player must flee from an invincible foe while dodging the obstacles in their path both with the analog stick and the face buttons. In these sections the player must use the analog stick to move around obstructions like crates and boxes and through narrow pathways. If a gap or low clearance is ahead, the game will prompt the player to push a specific face button to jump or duck. If the player takes too long to navigate the sequence, the enemy will catch the player and they will have to replay the sequence.