Objective: To investigate the influence of Tg737 gene overexpression on cell cycle and apoptosis in human hepatocellular carcinoma cell lines and the possible mechanism. Methods: Human hepatocellular carcinoma HepG2 and MHCC97-H cells were transfected with pcDNA3.1-Tg737 plasmid (Tg737 overexpression group) or empty pcDNA3.1 vector (empty vector group) mediated by liposome delivery, or cultured with liposomes alone (liposome group), respectively, with corresponding untreated cells as blank controls. Forty-eight hours later, the cell cycle status and apoptosis were analyzed by flow cytometry, nuclear morphological changes were examined by Hoechst 33342 assay, and the expression levels of cyclin A, Bax and Bcl-2 were detected by Western blot analysis. Results: Compared with corresponding blank controls, in Tg737 overexpression group of either HepG2 or MHCC97-H cells, the number of cells in the S stage and apoptosis rate were significantly increased (all P<0.05), and presented with the typical nuclear morphological changes of apoptosis, with significant upregulation of cyclin A and Bax and downregulation of Bcl-2 (all P<0.05); both HepG2 or MHCC97-H cells in empty vector group or liposome group showed no evident morphological changes of apoptosis, and the difference in all above indexes showed no statistical significance (all P>0.05). Conclusion: Tg737 gene overexpression can inhibit the cell-cycle progression and promote apoptosis of hepatocellular carcinoma cells, and the mechanism may be associated with the participation of Tg737 in regulating the signaling pathways involving cyclin A, Bax and Bcl-2.