I use my Ruger 22 Hornet on squirrles a lot. I love it!
I use a reduced load with the Speer jacketed 46 gr flat-nose bullet. I can't remember my exact loads (my notes are at home), but I have used Winchester 231, Unique, and Accurate Arms #5 in low amounts. They all seem to perform about the same - I like #5 the best because it flows through a powder measure so well.
MV is in the 1700-1800 fps range, but I think this is a bit too fast. I go for head shots as much as I can, and it messes the head up pretty good. One of these days I will try a lighter charge, to get the velocity down to the 1500 fps range and see how that works out. I think the flat nose on that bullet increases the killing power a lot.
Luckily, when sighted-in with these loads to be on at about 50 yd, and slightly high at 25, my hi-power loads are about 2" high at 100. Perfect! The hi-power loads are the Hornady 35 gr. V-max, with a maximum charge of Win. 296.