From High On Life Wiki

Story Difficulty

This difficulty is made for players to enjoy the game with minimal resistance from enemies. It will decrease enemy health and damage. It is intended for players who want to focus on the story aspect of the game.

Normal Difficulty

In Normal difficulty enemies health and damage will be higher than story difficulty. This will give player a little bit more of a challenge when playing through the game. Your first person shooter skills will be a great use in this difficulty mode.

Hunter Difficulty

Hunter Difficulty is made for players that look for a challenge. Enemies will have greater damage and health. Understanding mechanics of Bosses will be a great advantage to eliminating them. Aiming at weak points of enemies will be crucial at this game mode.