Hellboy and a rookie BPRD agent get stranded in 1950s rural Appalachia. There, they discover a small community haunted by witches, led by a local devil with a troubling connection to Hellboy's past: the Crooked Man.

Chev Chelios, a hit man wanting to go straight, lets his latest target slip away. Then he awakes the next morning to a phone call that informs him he has been poisoned and has only an hour to live unless he keeps adrenaline coursing through his body while he searches for an antidote.