A .22 round to the head is lethal very quickly. From about 50-100 feet, it goes in but does not exit. It tends to bounce around inside the melon doing all sorts of damage. Lights out.
They point out on the procedural shows ("Law & Order", "CSI:insert city here", "NCIS", etc. that the .22 is the hit-man's gun at close range. Deforms the bullet while bouncing around in the head, making it hard to match to the gun. But that could be H'wood over-dramatizing its effectiveness.
Assuming it hits an an angle where it penetrates, certainly. However, it’s not a sure thing.
There’s a reason nobody in the business of using a handgun in a serious defense capacity carries a .22lr, nor do any militaries issue weapons using that cartridge (nor have they ever).