Objective: To investigate the effects of rapamycin on the growth and apoptosis as well as DDAH2 expression in hepatocellular carcinoma cells. Methods: Human liver cancer HepG2 cells were exposed to different concentrations of rapamycin (0, 4, 20 and 100 nmol/L) for 48 h, and then the cell cycle and apoptosis were determined by flow cytometry, and DDAH2 expression was measured by Western blot analysis. Results: Compared with HepG2 cells in control group (0 nmol/L rapamycin), the HepG2 cells treated with various concentrations of rapamycin showed significant G1 phase arrest and increased apoptotic rate along with reduced DDAH2 protein expression (all P<0.05), with a certain concentration-dependent manner. Conclusion: Rapamycin can inhibit proliferation and promote apoptosis of liver cancer cells, and the mechanism may be associated with its down-regulaton of DDAH2 expression.