Survivin is a member of the inhibitor of apoptosis protein (IAP) family; it is overexpressed in most cancer tissues and induces resistance to chemotherapy. In this study, we investigated whether a short hairpin RNA (shRNA) targeting survivin can induce apoptosis and enhance chemosensitivity to cisplatin in squamous cell carcinoma of the tongue. Results showed that chemosensitivity to cisplatin was surviving dependent in three cell lines (Tca8113, Bca885, and MCF7); higher survivin mRNA expression levels were associated with lower sensitivity to cisplatin. A plasmid-containing survivin shRNA was constructed and transfected into cell line Tca8113. Survivin shRNA inhibited expression of survivin mRNA and protein (63% and 65% inhibition, respectively), significantly inhibited cell proliferation, and enhanced chemosensitivity to cisplatin (p < 0.05). Apoptosis and caspase-3 activity were induced when cells were treated with survivin shRNA and/or cisplatin. Survivin shRNA induced caspase-3-dependent apoptosis and enhanced chemosensitivity to cisplatin in these tongue squamous cell carcinoma cell lines.