Objective: By studying the influence of low-dose total body irradiation to proliferating cell nuclear antigens (PCNA), epidermal growth factor receptor (EGFR), erythropoietin (EPO) and vascular endothelial growth factor receptor (VEGFR) of tumor tissues in mice bearing S180 sarcoma, to further explore the mechanism of low doses radiation. Methods: S180 sarcoma cells were implanted subcutaneously into 58 male Kunming mice. Randomly these mice were divided into sham-irradiation (S) group and low-dose radiation (LDR) group. 12 days after implantation, the mice in LDR group were once delivered 75 mGy total-body 60Co γ-ray irradiation, while the mice in S group were left without irradiation. Then the mice in LDR group were executed at 6 h (LDR-6h group), 12 h (LDR-12 h group), 24 h (LDR-24 h group), 48 h (LDR-48 h group) and 72 h (LDR-72h group) after irradiation. Tumor tissues were weighed and histological observed. Immunohistochemical stain-ing was used to detect the expression of PCNA, VEGF, EPO and VEGFR of tumor tissues. Results: Though there was no significant difference between LDR group and S group in tumor weight, after irradiation the expression of PCNA and EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from S group. The expression of EGFR and VEGFR also decreased, and LDR-24h group was the lowest (P < 0.05). Conclusion: Seventy-two h after low-dose total body irradiation, there was no significant change in tumor size of mice bear-ing S180 sarcoma. Low-dose total body radiation decreased the expression of PCNA inhibiting tumor growth; reduced the expression of EGFR in tumor tissue impacting the signal transduction of tumor cells. The study also indicated that low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself.