Objective As a classical approach for hyperthermic ablation,microwave ablation (MWA) has been widely used in the treatment of tumors that cannot be removed by traditional surgery. MWA devitalizes the neighboring tissue and kills tumor cells by thermal diffusion. In the last two decades,this technique has been improved for treating malignant bone tumor in our institute. In situ ablation has already replaced en bloc resection and achieved satisfactory treatment outcomes. This study explores whether tumor cell death induced by MWA would cause the release of immunogenic tumor antigens and tumor-specific immune responses. Methods Three models of MWA were established using osteosarcoma cell lines from the mouse,rat,and human,respectively. The expression of immunogenic molecules was measured during in vitro and in situ ablation with different ablation time and group design. Results The injection of tumor vaccines made from tumor cells or supernatant treated with in vitro ablation resulted in substantial inhibition of tumor cell growth in tumor-bearing animal models. The CD₈+ T cells induced by vaccines played a key role in the process. The effector cells released cytokines,IFN-γ and TNF-α,to inhibit tumor cell growth and also trigger Fas/FasL-mediated apoptosis. Conclusions MWA-treated osteosarcoma cells can be used to induce specific antitumor immunogenic effects. Therefore,in situ MWA combined with immunotherapy provides an alternative treatment method for patients who have trouble due to their insensitivity to chemotherapy.