Objective: To develop a more effective induced-differentiation or -apoptosis therapy for treating oral squamous cell carcinomas. Methods: The combination of all trans retinoic acid (ATRA) and interferon-y (IFN-y) was tested for its antiproliferative activity against human tongue squamous cell carcinoma cell line (Tca8113 cells) in vitro. Clonogenic assay, MTT assay, and microscopic cell analysis were performed in this experiment. Results: The results show that the combination of ATRA and IFN-y can produce synergistic antitumor effects, resulting from induction of apoptosis, on Tca8113 cells. Conclusion: The combination of ATRA and IFN-y is a more effective induced-apoptosis therapy for treating oral squamous cell carcinoma.