Objective: To study the apoptosis mechanism of microwave ablation (MA) in tongue cancer Cal-27 cell transplanted tumor in nude mice. Methods: 20 nude mice with Cal-27 cell subcutaneously transplanted tumor were randomly divided into blank control group, 50 ℃ 1 min MA group, 50 ℃ 2 min MA group and 55 ℃ 2 min MA group (n = 5) respecitvely, and were treated with MA with indiated perameters respectively. The apoptosis of tumor cells was observed by HE staining. The expression of Caspase-3 and PCNA protein was detected by immunohistochemical SP method. Results: HE staining showed that microwave ablation induced apoptosis of the tumor cells. Immunohistochemical results showed that the expression of Caspase-3 protein was significantly up-regulated in the microwave ablation groups compared with the control group (P ＜ 0. 05), and the expression of PCNA protein was significantly decreased (P ＜ 0. 05) . In microwave ablation 55 ℃ 2 min group, the expression of Caspase-3 protein was increased more (P ＜0. 01), and the expression of PCNA protein was decreased more (P ＜ 0. 01) . Conclusion: Microwave ablation may inhibite the proliferation of tongue cancer cells by inducing apoptosis of the cells. The mechanism may be related to the up-regulation of Caspase-3 signaling pathway and down-regulation of PCNA signaling pathway.