.600 nitro express with the heaviest loads you can get.
It all depends on your firearms preference, your resources, and your home.
If you have no worries of over penetration, go with 12 gauge 00 buck if you want.
If you need one-shot-stops without the risk of over penetration, go with a good handgun with self defense/home defense ammo (glaser safety slug, Hornady ballistic tips, etc.)
It all depends on you.