Hades was first encountered by Smoosh in Chapter IV, where he was the first person encountered by the heroes in Hell. While speaking to smoosh, Hades mentioned that he was the former ruler of the Underworld, until it was taken over by Bobby Kotick (the devil) and renamed Hell, and that Hades now serves as an underling of Kotick. Hades then proceeded to leave the heroes to suffer the unimaginable horrors of Hell.
Later, Smoosh attempted to strike a deal with Hades, offering to help him overthrow Kotick and take over Hell. Hades is skeptical, but agrees to help the heroes if they can manage to hook him up with a "foxy" woman he met recently...who happens to be Hoar. While trying to prepare a romantic dinner for Hoar and Hades, Hoar has an allergic reaction to the food and vomits all over Hades's bachelor pad before running off. Enraged, Hades blames the heroes and locks them up in his dungeon.
After escaping and travelling to the final Circle of Hell, Smoosh manages to rescue Nico and defeat Kotick in the process. Hades, impressed by their achievement, gives Smoosh one of the items on Nintendoki's list (a piece of lava from the centre of the earth) and sends them back to the world of the living. Hades then takes over Hell and changes its name back to the Underworld.
Although he appeared to have now been friends with Smoosh, Hades was later seen speaking with Segami, implying that he may be allied with him and Doosh, meaning that smoosh may have to fight Hades in the future.