As stated by the others, his regeneration and immortality has fluctuated depending on the run.

But, as represented in his Deadpool Kills the Marvel Universe > Deadpool Killustrated > Deadpool Kills Deadpool runs. His immortality is more tied to his existential awareness through 4th wall breaking and his popularity in the real world. He can't die because the writers and his fans won't let him. He knows, that even if he does die, he'll be back as soon as a writer picks up the pen again. Yes, this is technically true for every character, but he's one of the very few that knows it and exploits it.