We currently use a combination of a regular and an "advanced/fancy" endpoint malware protection, in the advanced malware app, I can feed a SHA256 hash of an executable into the advanced platform and it will block execution of the given executable.
Can I do the same (blacklisting, not whitelisting) with AppLocker?
Yes, you can block/prevent/deny executables with Applocker, providing that the client OS supports Applocker.