Doctor Who: 9 Ways To Kill The Doctor Permanently
2. The Chameleon Arch
Time Lords are obviously really hard to kill, but what if you could change them into something that's a bit more, well... mortal?
The Chameleon Arch was first introduced in Series 3's Human Nature, and, as the Tenth Doctor explains, its purpose is to change "every single cell" in his body, completely rewriting his biology and turning him into a different species.
In this case, he turns himself into a human, meaning that every single advantage of being a Time Lord is completely stripped away from him - his vast knowledge of the universe, his more durable body, and crucially, his ability to regenerate. As such, it would be pretty easy to permanently kill the Doctor while he's in this human form.
It's not clear how widespread the Chameleon Arch technology is, but if a villain were to break into the TARDIS somehow (which seemed pretty easy to do at the end of Series 12), maybe they could turn the Doctor into a human, and murder them on the spot.
It's a bit of a convoluted plan, sure, but it's probably quicker than murdering your way through countless regenerations.