Abstract: Objective To investigate the role of CXC chemokine receptor 4(CXCR4) signal effects on the expression of alpha fetoprotein(AFP) in human hepatoma cells, HepG2, and effects of AFP on AMD3100 induced apoptosis of HepG2 cells. Methods The effects of AMD3100, an antagonistic agent of CXCR4 ligand, on proliferation of human hepatocellular carcinoma cells HepG2 was detected by MTT. Western blot was applied to identify the expression of AFP and CXCR4. Small interference RNA was used to suppress expression of AFP in HepG2 cells, and apoptosis of HepaG2 cells were analazed by fl uorescent microscopy and fl ow cytometry. Results Here we demonstrated that high concentration (>1.0μg/ml) of AMD3100 might inhibit proliferation of HepG2 cells. AMD3100 had a function to down-regulate the expression of CXCR4 and AFP in HepG2 cells.The results also indicated that the expression of AFP had synergies with AMD3100 in inducing apoptosis of HepG2 cells in vitro. Conclusion HepG2 cells were tolerant to apoptosis induced by AMD3100 through expressing AFP.