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Osteosarcoma is an aggressive bone cancer that frequently metastasizes to the lungs. The cytotoxicity of most chemotherapeutics and targeted drugs in the treatment of osteosarcoma is partially lessened. Furthermore, there is a poor response to current chemo- and radiotherapy for both primary lesions and pulmonary metastases of osteosarcoma. There is a clear need to explore promising drug candidates that could improve the efficacy of osteosarcoma treatment. Autophagy, a dynamic and highly conserved catabolic process, has dual roles in promoting cell survival as well as cell death. The role of autophagy has been investigated extensively in different tumor types, and a growing body of research has highlighted the potential value of using autophagy in clinical therapy. Here, we address significant aspects of autophagy in osteosarcoma, including its functions, modulation, and possible therapeutic applications.