How can I beat the Guardian of Yendor?

The Guardian is easily defeated if you have at least a couple of powerful magic wands. Namely, a +5 Staff of Fireballs, +5 Staff of Lightning, or even the Staff of Fiery Doom are very effective against it. Also, the Guardian is not immune to poison. If you manage to find an item that makes you immune to poison, you can severely weaken the Guardian by hiding in a small room (with no open flames) and filling it with poison gas repeatedly. The Guardian will keep reappearing in that room looking for you, taking poison damage all the while.

Going toe-to-toe in melee combat is usually inadvisable. However, if you make a +5 Staff of Life Steal (by taking the Necromancer's staff & using 2 enchant scrolls on it,) you can repeatedly hit the Guardian with a powerful weapon, (taking equal damage in the process) and heal up with the staff.

Be sure to have at least a few Scrolls of Recharge as well!

Bows were once effective, yet updates seem to have added arrows to the Guardian's many immunities.

Now get back down there & take the bastard down! ;-)

You don't defeat him, you grab the amulet and run all the way back to start, that's how you win the game