Either one will work great. I heve used both. Right now I am using a 20 guage and Remington Express 2.75" #5 shot. A .410 with 3" #4 shot might even be better. Sometimes my 20 eats em up if they're just a little too close or if I have to hit them more than once. Oveall though I really enjoy hunting them with a shotgun. It's not quite as challenging as with a .22 but a heck of a lot of fun. If you're not eexperienced hunting squirrels I would recommend a shotgun in either .410 or .20 guage with the ammo I mentioned above. Besides I use the shotgun for deer and hog too so if a morning of deer and hog hunting is not going too good I can always just switch shells and get an hour or so of squirrel hunting in to make myself feel better.