Abstract: Objective:To investigate the effects and mechanism of cyclooxygenase-2(COX-2) and vascular endothelial growth factor (VEGF) inhibition of human hepatocellular carcinoma (HCC) implants in nude mice by Interferon-α-2b (IFN-α-2b) therapy. Methods: Nude mice bearing human HCC were randomized into the following groups 10 days after implantation of hepatoma cells: saline (control); experiments (group A, IFN-α-2b 10 000 IU; group B, 20 000 IU and group C, 40 000 IU administered s. c.daily, respectively). The growth conditions of xenograft tumor were observed after 35 consecutive days. The COX-2 and VEGF expression of tumors were detected by immunohistochemistry. Microvessel density (MVD) was counted by endothelial cells immunostained by anti-CD34 antibody. The TUNEL assay was used to examined the apoptosis alteration of tumor cells in nude mice after treatment with IFN-α-2b. Results: The IFN-α-21)-treated tumors were significantly smaller in volume and lower in weight than those in control group (P<0.01). Compared with the control group, the proteins of COX-2 and VEGF expressed more lower in the IFN-α-21)-treated tumor cells (P<0.01). The amount of MVD in the IFN-α-21)-treated tumor tissues was significantly lower than that in control group. The apoptosis index (AI) of tumor cells with IFN-α-2b treatment was markedly higher than that of control group (P<0.01). The group at the dose of 20 000 IU/d had higher inhibition rate of tumor growth, lower expression of COX-2 and VEGF, lower amount of MVD and higher AI in comparison with the groups at the dose of 10 000 IU/d and 40 000 IU/d (P<0.05), but there was not significant between the group at the dose of 10 000 IU/d and that of 40 000 IU/d(P>0.05). Conclusions: The mechanism of the inhibition of the implanted tumor growth and induction cell apoptosis with IFN-α-2b treatment may be associated with the downregulation of COX-2 and VEGF expression. There was a dose-effect relationship at allthree doses; the medium dose(IFN-α-2b, 20000 IU/d) was prominent in the inhibition of tumor growth.