14-3-3ζ protein as the central regulatory factor of intracellular signal transduction process plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). Several studies indicated that the expression of 14-3-3ζ protein is elevated significantly in HCC, and participate in various cellular processes such as cell proliferation, invasion, and apoptosis. Additionally, by interacting with a multitude of target proteins, 14-3-3ζ protein can regulate a variety of signaling pathways that contribute to the occurrence and development of HCC, this suggests that it may be used as a potential biomarker for the early diagnosis, prognostic prediction, chemoresistance and treatment of HCC. The overexpression of 14-3-3ζ protein is associated with the increased risk of recurrence and metastasis and the reduced survival rate of HCC patients. The authors review the impact of 14-3-3ζ protein on regulation of expression, biological function and the occurrence and development of HCC and the relevant research progress.