Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. However, the prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear. We used immunohistochemistry to evaluate the presence of tumor-infiltrating FoxP3⺠T-cells and CTLA-4⺠cells in four distinct histological compartments (tumor parenchyma and stroma at the tumor center, and parenchyma and stroma at the invasive front) and assessed the association between the prevalence of these cells and the histopathological status of 137 patients with OSCC. Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of FoxP3⺠T-cells in the parenchyma of the invasive front. Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of CTLA-4⺠cells in the parenchyma of the invasive front. The presence of FoxP3⺠T-cells in the parenchyma of the invasive front may be a useful prognostic factor. Our results indicate that FoxP3⺠T-cells may exert site-specific anti-tumor effects but may not play an immunosuppressive role in OSCC. In addition, our results suggest that CTLA-4.sup.+ cells suppress the function of FoxP3.sup.+ T-cells and promote anti-tumor immunity in OSCC.