The Key of Destruction is required to open the first red portals in the Pandemonium Event and can only be found from certain boss monsters, and only on Hell difficulty.
Get the Key of Terror from The Countess, the Key of Hate from The Summoner, and the Key of Destruction from Nihlathak. It's a good idea to have 3 of each key before beginning the second stage of the Pandemonium Event, for reasons explained in the Pandemonium Event article.
The keys look identical, and can only be discerned between by hovering on them to see their name.
Key of Destruction
Nihlathak sometimes drops this key, but only on Hell difficulty. He's found at one end of the four-pointed Halls of Vaught, the lowest of the three Halls levels reached through Anya's portal in Harrogath, in Act Five.