The expression of mIL-12 p70 in the supernatant of cultured COS-7 and B16 melanoma cells transfected with pNEgr-mIL-12 and the tumor growth rate in mice after gene-radiotherapy with pNEgr-mIL-12 plasmid and different doses X-irradiation were observed. The expression of mIL-12 p70 in the supernatant of COS-7 and B16 melanoma cells were most prominent after X-irradiation with 1.5～2.0 Gy, and doses as low as 0.05 Gy also showed a stimulatory effect. Time-course studies showed that the expression of mIL-12 p70 in the supernatant of COS-7 cells reached its peak at 4 h after irradiation and a progressive increase in expression of mIL-12 p70 in the supernatant of B16 melanoma cells was observed over the study period of 72 h. In vivo, the injection of pNE-mIL12 recombinat plasmid into tumor followed by local X-irradiation one or three times could inhibit the growth of B16 melanoma implanted in C57BL/6J mice and the surviving days of tumor-bearing mice was delayed. It will provide an experimental basis for planning effective clinical gene-radiotherapy of cancer.