Objective：To investigate the inhibitory effect of adenovirus-mediated herpes simplex virus-thymidine kinase (TK) gene combined with α-IFN on renal clear-cell carcinoma. Methods: Adenovirus containing suicide gene TK, in combination with GCV or α-IFN, was used to treat human renal clear-cell carcinoma cell line 786-0, and the in vitro cytotoxic effects against 786-0 were evaluated using MTT method. The subcutaneous transplantation model of 786-0 cells was established with nude mice. Adenovirus containing TK gene was injected intratumorally and the GCV (50 mg/kg) was injected intraperitoneally; α-IFN (104 U/L) was injected intratumorally in combined therapy. The growth of tumors was observed after treatments. Results: The survival rate of 786-0 cells was (35.07±1.43)% in the TK+GCV+α-IFN group, (68.57±1.41)% in the TK+GCV group and (68.65±1.45)% in the α-IFN group ( P=0.000). There was an obvious synergic effect between Ad-TK and α-IFN in inhibiting 786-0 cells. Ad-TK combined with GCV and α-IFN significantly suppressed the growth of 786-0 cells growth in nude mice model.Conclusion: Adenovirus-mediated TK plus prodrug GCV combined with α-IFN has obvious therapeutic effect in treatment of human renal clear-cell carcinoma.