Indeed, we demonstrate herein that silencing of PRPF8 can reduce the tumorigenic capacity of different liver cancer cell lines (HepG2, Hep3B, and SNU-387); reduce proliferation, migration, and the formation of colonies and tumorspheres in vitro; and suppress tumor growth in vivo in a preclinical HCC model. This evidence concerns the gene PRPF8 and hepatocellular carcinoma.