A reference to Hirohiko Araki's long running manga (and anime) series Jojo's Bizarre Adventure. Usually pertaining to things simular to or referencing Jojo's Bizarre Adventure themes such as floating or exploding Kanji, posing that covers the face and aesthetic of both the show and manga.
Increasingly used on the internet, the phrase "Is that a JoJo reference?!" refers to the anime JoJo's Bizzare Adventure. Since the anime is used in a lot of memes, when people spot something related to JoJo in a meme they tend to ask if it is a JoJo reference.
A Jojo reference is a reference to something in the Jojo's Bizarre Adventure Manga. Sometimes, people make Jojo references on accident, or on purpose. Like someone saying "I refuse." with the Rohan face, Or making a donut Joke.