22 with subsonic rounds. Other rounds too loud scares the other squirrels into jumping and hiding....with short hollow points squirrels often stay put allowing a still target for the remaining squirrels in the same tree on in the immediate area.....Be sure to test for good groups....kill zones on a squirrel are small.
I hunt with the 22LR and the 17Mach 2. I hunted yesterday with the 17 Mach 2. Managed 3 grays for the afternoon hunt. Two head shots and one neck shot. The biggest advantage the 17HM2 has over the 22LR IMO is the fact that it shoots much flatter. The other at least in my experience is the quarry is DRT more often with the 17. Confine yourself to head and neck shots with either one. I still use my 22LR but the 17 Mach 2 is probably the finest round ever designed for squirrel hunting.