[Ovrlndnsea]

It depends on whether or not you are a mage or a meleer. I'll assume that anyone who isn't one of them knows how to play the game well enough to not need my advice.

If you are a meleer, you need resists to paralysis, death, and fire, at the very least. Cold, shock, slow, and curse resists would also be highly useful.

If you are a mage, toss fireballs (or whatever) at them from a distance till they die. Dodge all spells before they get to you.
If skulls are next to the entrance of a room, write a command like "go north;cast fireball west;cast fireball east;go south" if moving north and south make you enter and exit the room.