E3 ubiquitin ligases participate in the pathogenesis and progression of tumors by regulating key proteins involved in numerous biological processes in cells. RING-finger E3s, as the largest E3-ligase family, play important roles as tumor suppressors or oncogenes in hepatocellular carcinoma (HCC) under certain circumstances. Here, we summarize the abnormally expressed RING-finger E3s and their related mechanistic effects in HCC, and describe the application potential of therapeutic approaches targeting RING-finger E3s in HCC.