In our study, our results showed that CyclinD1、P53 and Rb were increased and P27 was decreased in variant type group, which suggested that E167K polymorphism of TM6SF2 gene may change the cell cycle of hepatocellular carcinoma cell HEPA 1–6 through up-regulatating CyclinD1、P53 and Rb and down-regulatating P27. Here, TM6SF2 is linked to hepatocellular carcinoma.