Background: Advanced hepatocellular carcinoma (HCC) patients undergo significant tumor growth and metastasis.Here,we investigated bufalin for treating HCC,which exhibits anti-tumor activities in many tumor cell lines.Method: In our experiment,HCCLM3-R cells were injected into nude mice to form subcutaneous human HCC tumors that were implanted into the liver to establish orthotopic transplantation tumor models.Bufalin was injected intraperitoneally at 1 or 1.5 mg/kg.LY294002 (100 mg/kg),a potent inhibitor of Akt which reduced the levels of pAkt in HCCLM3 cell lines,was injected intraperitoneally into one group thrice weekly.