Objective:To study the anti-tumor effect of repeated low dose pEgr-IFN-γ gene-radiotherapy in mice bearing melanoma and its immunologic mechanism. Methods:The pEgr-IFN-γ plasmids packed by liposome were injected locally into tumors, and then the tumors was irradiated by X-ray 36 hours later. The tumor growth rate at different time and mean survival period of the mice were observed. The IFN-γ mRNA level in tumors was detected by RT-PCR 3 days after irradiation. The concentration of IFN-γ in serum were detected by ELISA. The immunologic indexes was detected 15 days after irradiation. Results: The tumor growth rate of the mice in gene-radiotherapy group with pEgr-IFN-γ and 5 Gy X-ray irradiation four times were lower significantly than that with pEgr-IFN-γ and 20 Gy X-ray irradiation 9~15 days after irradiation and their mean survival period were longer. The IFN-γ mRNA level in tumors of the mice in gene-radiotherapy group were higher than that in reconstruction plasmids group significantly 3 days after irradiation; The IFN-γ concentration in serum of the mice in gene-radiotherapy group were higher than that in reconstruction plasmids group and control group 1 and 3 days after irradiation; NK cytotoxic activity, IL-2 and IFN-γ secretion activity of the mice in gene-radiotherapy group were higher than that in 20 Gy X-ray irradiation group 15 days after irradiation.Conclusions: The anti-tumor effect of repeated low dose gene-radiotherapy was better than that of high dose gene-radiotherapy for only once. By inducing higher expression of IFN-γ gene in the tumors, pEgr-IFN-γ gene-radiotherapy could increase the concentration of IFN-γ in serum, and therefore the body’s immunologic function and anti tumor ability were enhanced.