The Keys of Hades are magic "keys" owned by the god Hades. They have the power to "seal" or "free" people in the Underworld, which means someone can bring someone back from or send someone to the Underworld or Tartarus using the keys.
One of the keys was placed inside the Sword of Hades. It is said that one touch of the sword can send or release a soul to and from the Underworld. The sword was stolen and Persephone feared that anyone who possessed it could release anyone from the Underworld. After Percy Jackson retrieved it through the events of Percy Jackson and the Sword of Hades, it is revealed that Hades had no part or knowledge in its creation. Knowing it would upset the balance of power between the Big Three, he was angry with Persephone for having it forged and swore an oath never to use it against the Olympians. Despite his anger about it's creation, it is assumed that he had used this same sword, the key included, in the Battle of Manhattan.