Objective: This study investigated whether T cells immune suppression exist in Oral Squamous Cell Carcinoma (OSCC) patients. We also investigated peripheral cellular immune responses to recombinant adenovirus vectors expressing wild type p53 (rAd-p53) in oral cancer patients. Materials and methods: We analyzed distributions of peripheral blood T cell subsets in OSCC patients group (OG, n= 80) and healthy people group (HG, n= 79) by flow cytometry. A cohort of 42 oral cancer patients was divided into the experiment group (EG, n= 18) and the control group (CG, n= 24), depending on whether patients received rAd-p53 gene therapy. Peripheral blood were collected before and after operation, then flow cytometric counts were performed to detect the transformations of the frequencies of peripheral blood T lymphocyte subsets. Results: OSCC patients show significantly lower percentages of CD3+CD4+, CD4+CD45RA+, CD8+CD28+, and CD3+HLA-DR-cells, and significantly higher percentages of CD4+CD45RO+, CD4+CD25+FoxP3+, CD8+CD28-, and CD3+HLA-DR+cells. And advanced stage OSCC patient show a significantly higher proportion of CD8+CD28+cells than early stage patients. After treatment, the oral cancer patients received surgery alone had a decreasing tendency in CD3+CD8+cells. But the rAd-p53-treated patients had no significant fluctuations in the proportion of any T cell subsets. Conclusion: OSCC patients show a suppressive T cells immune state in general. Surgery alone may weaken anti-tumor immunity within a short time period, whereas regional injection of rAd-p53 as adjuvant therapy for cancer surgery could enhance anti-tumor immunity.