This study aimed to analyze CD8+ and CD4+ cells in oral squamous cell carcinoma and to correlate it with prognostic indicators. The sample was composed of 50 cases. Clinical data and histologic grade of malignancy were obtained. Specimens were submitted to immunohistochemistry. Cells were counted in 10 fields at the tumor invasion front and expressed as median. CD8+ cells were more frequent in nonmetastatic lesions (18.5) and in low-grade specimens (18.2) (P<0.05). CD4+ cells were equally distributed in nonmetastatic and metastatic lesions (4.5). In addition, they were slightly more frequent in low-grade lesions (4.7). None of these correlations were significant (P>0.05). CD8+/CD4+ ratio was higher in cases without metastasis (3.57) and in low-grade lesions (3.62) (P>0.05). Probably, CD8+ cells are the most effective and important cells in the host immune responses against oral squamous cell carcinoma. In addition, CD4+ cells could indirectly influence the host protection through regulation of CD8+ recruitment and activation.