To investigate anti-tumor effect of bufalin on the orthotopic transplantation tumor model of humanhepatocellular carcinoma in nude mice. Methods: BEL-7402 cells of human hepatocellular carcinoma were inoculated to formsubcutaneous tumors in nude mice by subcutaneous injection. Then the subcutaneous tumors were implanted into the liver ofnude mice, and the orthotopic transplantation tumor models of human hepatocellular carcinoma were established. Seventy-fivemodels were randomized into 5 groups ( n = 15). Bufalin was injected intraperitoneally into the 3 groups at dose of 1.5,1 and0.5 mg/kg for day 15 - 24, respectively. NS group were injected equal volume saline as above and adriamycin were injectedintraperitoneally into ADM group at dose of 8.0 mg/kg for day 15. Ten mice in each group were killed at day 25 and detectedon morphological and ultrastructural changes in myocardium, brain, liver, kidney and tumor tissues by pathology and electronmicroscope. The survival time in each group were observed. Results: The tumor volumes in each group of bufalin were re-duced significantly compared with NS group ( P＜0.01), the survival time were prolonged in group Bu 1 and Bu 2 comparedwith NS group (P＜0.05), and tumor tissues were mainly necrosis in severe or moderate degree in Bu 1, Bu 2 groups, andmild degree or moderate degree in Bu 3 group. No morphological changes were detected in myocardium, brain, liver and kid-ney tissues, respectively. Apoptotic characteristics could be seen in tumor tissues of group Bu 1 and group Bu 2. Conclusion:Bufalin has significant anti-tumor effects on the orthotopic transplantation tumor model of human hepatocellular carcinoma innude mice without marked toxicity. To guide cell apoptosis may be one of its anti-tumor mechanism of bufalin.