Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second major cause of cancerous deaths in the world, accounting for 80-90% of all cases of liver cancer with an assessed global incidence of 782,000 new cases and approximate 746,000 deaths in 2012. Preoperative laboratory data (des-γ carboxyprothrombin (DCP), α-fetoprotein (AFP), Indocyanine green retention 15 min (ICG-R15), and γ-glutamyl transferase (GGT)) should be completely assessed before deciding a treatment and predicting prognosis in order to improve the prognosis for patients with HCC. A few recent studies have suggested GGT as an independent prognostic indicator in cases with HCC. And the data of our and other research teams revealed that combination of GGT and ICG-R15 or other factors may improve the efficiency of GGT as a prognostic predictor. In addition of clinical studies, a few mechanistic studies had been performed and GGT was suggested to promote tumor progression and poor prognosis through inducing DNA damage and genome instability, releasing reactive oxygen species to activating invasion-related signaling pathway, blocking chemotherapy, regulating microRNAs, and managing CpG island methylation. Although there were a few mechanistic studies, further and accurate researches were still in need.