It seems, the Ao Oni cannot die and can only be locked inside the school that looks like a mansion. The Ao Oni is a giant headed purple monster that has transformed from a human to an oni and it eats people or bites their heads off. The origin of the Oni is a blue flower that takes a form of a female to seduce its victim, in this case a male and then it will turn the guy into an Oni in the end of his lifespan. But, of course, the male, during this time, would probably be sleeping with multiple women or girls and then let them carry the egg of the blue flower and Ao Oni, therefore producing for chances for more Ao Oni to be in the world which would be a nightmare. The male, at the end, will have this private parts rot and fall off and then he melts or becomes a deformed figure and then taking on the form of another Ao Oni. [This is what the anime said, not sure about the fandom]
True, that destroying this blue flower can probably destroy the Oni, but the blue flower in the anime adaptation took on the form of the school nurse and these flowers can also make you think they are human and wipe your memories, which won't help in exterminating all the flowers. So, even if all the flowers have been destroyed or burnt, the Ao Oni can't be destroyed since the flower can just clone itself into multiple human forms. However, it seems that the Ao Oni doesn't kill at random, it only kills those who try to investigate or search for it, like a myth or rumor, if you believe in it, it might come true and it may haunt you afterwards.
Also, you should read the wiki fandom or TV tropes on this, I don't really know anything.

I kind of have some mixed feelings for this animation though. The quality isn't really the best, it is locked at 360p video quality. The horror scenes are worth it though, not really scary as such, it doesn't look very gory or anything, just there is too much blood in it, such as when the Ao Oni hunts its targets or victims, the blood just seems overly exaggerated or too much. I kind of wish there were more movies though, it's only a one hour movie and I'm pretty sure the live action one had more movies so I kind of wish there was a sequel to it and hopefully one where they actually destroy the Ao Oni if possible.

Also, marked as spoiler, I say way too much, and most of them are references and facts.