To investigate the role of Porphyromonas gingivalis (P.g) in the tumor microenvironment of oral squamous cell carcinoma (OSCC) and provide new insights for OSCC treatment.The murine squamous cell carcinoma cell line SCC7 was cultured in vitro, and a tumor-bearing model was established with C57BL/6 mice. Experimental mice were randomly assigned to the P.g activation group and the control group (n = 5 per group) based on the principles of randomization and control. After 16 days of feeding, the mice were sacrificed, and the weight and volume of the tumors in the two groups of mice were recorded. Immunohistochemistry was performed to analyze the expression levels of CD4+ T cells, CD8+ T cells, transforming growth factor-β (TGF-β), interleukin-10 (IL-10), interferon-γ (IFN-γ), E-cadherin, N-cadherin, Twist, vascular endothelial growth factor (VEGF), CD31, and Ki67 in the tumor tissues. Flow cytometry was performed to examine the tumor samples from the two groups of mice, and to quantify the proportional differences of CD4+ T cells, CD8+ T cells, as well as CD69+ and CD103+ on T lymphocytes from the samples.The immunohistochemistry results showed that the expression of CD4+ T cells and their function-related cytokines in the tumor tissues of the activation group was higher than that of the control group, and the differences were statistically significant (P < 0.05). According to the flow cytometry results, the proportion of CD8+ T cells in the tumor tissues of the activation group decreased, and the proportion of CD103+CD8+ T cells, which played an anti-tumor immune role, also decreased, with the differences being statistically significant compared with the control group (P < 0.05). In addition, the expression of all the cytokines associated with malignant tumor phenotypes in the activation group increased, and the differences were statistically significant compared with the control group (P < 0.05).This study verified through animal experiments that by enhancing the infiltration of CD4+ T cells and suppressing the immunosuppressive function of CD8+ T cells in the OSCC tumor microenvironment, P.g enables tumor cell immune escape and accelerates epithelial-mesenchymal transition, angiogenesis, and tumor cell proliferation.© 2025《四川大学学报（医学版）》编辑部 Copyright © 2025 Editorial Office of Journal of Sichuan University (Medical Sciences).