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AIM: TO evaluate the effects of interferon-α-2b (IFN-α-2b) on expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human hepatocellular carcinoma (HCC) inoculated in nude mice and to study the underlying mechanism of IFN-α-2b against HCC growth.METHODS: Thirty-two nude mice bearing human HCC were randomly divided into four groups (n = 8). On the 10th day after implantation of HCC cells, the mice in test groups (groups A, B and C) received IFN-α-2b at a serial dose (10000 IU for group A, 20000 IU for group B, 40000 IU for group C sc daily) for 35 d. The mice in control group received normal saline (NS). The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and West blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b.RESULTS: Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group (P< 0.01), and the tumor growth inhibition rate in groups A, B and C was 27.78%, 65.22% and 49.64%, respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group (P<0.01). The apoptosis index (AI) of tumor cells in the IFN-α-2btreatment groups was markedly higher than that in the control group (P<0.01). Group B had a higher inhibition rate of tumor growth, a lower expression level of COX-2 and VEGF and a higher AI than groups A and C (P<0.05), but there was no significant difference between groups A and C.CONCLUSION: The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20000 IU/d.