Background Despite diagnostic and therapeutic advances in head and neck cancer, the 5-year survival of patients with oral cancer has not improved adequately in the last 30years. Several recent studies indicate that specific targets for immunotherapeutic approaches can be useful in the control of cancer. There is considerable interest in the expression of cancer testis antigens in human cancers since they may serve as the basis for an immunologic approach to therapy. Methods This study involved immunohistochemical analysis of 63 patients with oral squamous cell carcinoma (SCC) and was carried out using antibodies for MAGE-A4, MAGE-C1, NYESO-1. Fisher’s exact test and log-rank test were used to evaluate the results. Results The expression of the MAGE-A4 and MAGE-C1 were 56.5% and 47.8% without statistical difference in studied variables and survival. Conclusion The expression of at least 1 CTA was present in 78.3% of the patients, however, without correlation with clinicopathologic variables and survival. Our data indicate that cancer testis antigens could be valuable vaccine targets in oral tumors, especially in those with a worse prognosis.