I've shot 7-1/2's and 8's. When I tried 6's they blew the squirrels up. Of course I would hunt with someone, one of us would shoot the nests with a sling shot to run the squirrels out, the pop them with the shotguns. No 8's and 7-1/2's didn't do as much damage, and the wherent too far away. A lot of times, I would watch them run up a tree and stick their head out from behind to see the danger, and I would shoot them in the head.
All that being said, a 22lr does good, and at a little longer range. Just be sure of your background.