Abstract: Objective To investigate the clinical significance of CD4+CD25+Foxp3+ regulatory T cells expression in peripheral blood and cancer tissues of OSCC patients. Methods Thirty cases of oral squamous cell carcinoma patients were selected as experimental object. They were divided into two groups, group A(clinicalⅠ and Ⅱperiods) and group B(clinical Ⅲ and Ⅳ periods) according to clinical period. The control group was 10 healthy volunteers (group C). Peripheral blood specimens of all groups were collected in the morning with an empty stomach. Expression of CD4+CD25+Foxp3+ regulatory T cells, mononuclear cells of CD80, CD86 and HLA-DR were detected in peripheral blood by fl ow cytometry. The infi ltration of Foxp3+ regulatory T cells in surgical specimens tissues of the experimental group and control group were determined by immunohistochemistry. Results The proportion of CD4+CD25+Foxp3+ T lymphocytes in CD4+ T lymphocyte in the three groups were (2.80 ± 0.90) %,(5.09 ± 1.72)% and(0.57 ± 0.15)%, respectively, with the statistically signifi cant difference(P = 0.000). The expression of co-stimulatory molecules CD80+CD86+, CD80+HLA-DR+ and CD80+HLA-DR+ in the mononuclear cells of group A and group B were obviously lower than that in group C. The proportion of CD4+CD25+Foxp3+ regulatory T cells and the expression rates of CD80+CD86+, CD80+HLA-DR+ and CD86+HLA-DR+ were tested by a linear correlation analysis, and the obtained correlation coeffi cients were -0.512, -0.430, -0.461, respectively, all of which were statistically signifi cant. Immunohistochemistry results showed that Foxp3 regulatory T cells were mainly distributed in the lamina propria tumor interstitial. The Foxp3+ regulatory T cells in the well-differentiated and moderately differentiated oral squamous cell carcinoma were less than poorly differentiated oral squamous cell carcinoma. The difference was statistically signifi cant. Conclusion The detection of CD4+CD25+Foxp3+ regulatory T cells in the peripheral blood and tumor tissue of patients with oral cancer is contributed to assess the antitumor immunity levels, disease progress and prognosis and evidence clinical biological therapy.