Why would anyone even consider the .22 LR for self-defense? Using the pipsqueak rounds when your life hangs in the balance may seem similar to the "Charge of the Light Brigade," taking the approach that, "Theirs not to reason why. Theirs but to do and die." That kind of thinking is unacceptable.
The fact is, .22 LR is, will and has been used extensively for self-defense—probably more often than you think. Rifles and handguns chambered for the rimfire cartridge are affordable, compact and the most common of all firearms. They have been the gun behind the door in American households for more than a century. They're easy to shoot, don't make a lot of noise and don't cost an arm and a leg to feed.
Why are they often used for self-defense? Well, why do you pick your nose with your finger? It's convenient at the time.
A .22 LR is the only gun some people own. That doesn't mean it's the most appropriate. I've driven nails with a crescent wrench and smashed my finger, used a knife as a pry bar and cut myself and even tried to move snow with a dirt shovel and been down in the back for a week. We can all agree there's almost always a better choice for self-defense. The question is: When, if ever, is the .22 LR a good choice and just how effective is it?
I asked Ed Head, operations manager at Gunsite, for his opinion. He said, "Since the first rule of gunfighting is to have a gun, any gun is better than none at all. The little .22 LR may actually be better than some larger calibers, depending upon the ammunition selected. For example, I would think a high-velocity .22 cartridge like the Stinger might be a better choice than a .25 ACP loaded with FMJ rounds."
According to the book "Stopping Power, a Practical Analysis of the Latest Handgun Ammunition," by Evan Marshall and Ed Sanow, Head is right. Marshall and Sanow found .22 LR Stinger ammunition was 58 percent more effective at producing one-shot stops than any of the FMJ .25 Auto loads.
https://www.shootingillustrated.com/articles/2010/10/26/22-lr-for-self-defense/