MAGE-A antigens are a subgroup of cancer/testis antigens that are exclusively expressed in malignant cells. Only scarce information on the function of MAGE-A antigens is available. There is some evidence that they may influence the response to chemotherapeutic drugs. This study aimed to evaluate the impact of the MAGE-A antigen subgroups MAGE-A2, −A3, −A4 and −A6 on oral squamous cell carcinoma cell lines treated with docetaxel and paclitaxel. Five oral squamous cell carcinoma cell lines were characterized for their quantitative expression of MAGE-A2, −A3, −A4 and −A6. The cell lines were treated with concentrations ranging from 0.025 to 0.8 μM of docetaxel and paclitaxel. The amount of viable cells after 24 and 48 h was measured. The measurements were statistically correlated with MAGE-A expression. All cell lines responded to docetaxel and paclitaxel. One cell line showed a statistically significant weaker response to the taxane treatment. This cell line was the only one that expressed MAGE-A4. MAGE-A4 has a statistically significant impact on the tumour response to docetaxel and paclitaxel in oral squamous cell carcinoma. This may influence treatment options and the course of the disease. Therefore, patients should be evaluated for MAGE-A4 expression before treatment with taxanes.