I can't count the squirrel and rabbit that have fallen to my single six over the years. I also use a Ruger target auto and even a little Bearcat! You need to do some extensive practice to make sure you can hit that walnut sized head, take your time and squeeeeeeezzzzzzeeeee! The hammer drop on the single six can throw you off a little so there is not substitute for practice. These guns can easily be scoped as well and this can be a definite aid in squirrel hunting. But if you scope, realize that the close shots will be very difficult. You will shoot under a squirrels head at about 10 or 12 feet if you don't compensate for the mounting of the scope over the bore. I like open sights.
Last year while I was muzzleloading hunting for squirrel, I had a big fat fox squirrel scamper dow the tree I was standing beside. Way too close for the long rifle, I drew my little bear cat and dropped it at my feet. Half an hour later, I had it happen again. Another shot and two squirrel lay side by side and I hadn't even fired the long rifle. Squirrel are a blast when you stand hunt'em like deer. Get in an acorn or walnut or pecan area and sit quiet. You'll eventually have one come so close you can pot them without effort.
Dan C