Osteosarcoma (OS) is the most common primary bone malignancy, mainly affecting children and adolescents. Currently, surgical resection combined with adjuvant chemotherapy has been standardized for OS treatment. Despite great advances in chemotherapy for OS, its clinical prognosis remains far from satisfactory; this is due to chemoresistance, which has become a major obstacle to improving OS treatment. Autophagy, a catabolic process through which cells eliminate and recycle their own damaged proteins and organelles to provide energy, can be activated by chemotherapeutic drugs. Accumulating evidence has indicated that autophagy plays the dual role in the regulation of OS chemoresistance by either promoting drug resistance or increasing drug sensitivity. The aim of the present review was to demonstrate thatautophagy has both a cytoprotective and an autophagic cell death function in OS chemoresistance. In addition, methods to detect autophagy, autophagy inducers and inhibitors, as well as autophagy-mediated metastasis, immunotherapy and clinical prognosis are also discussed. Contents 1. Introduction 2. Methods of detecting autophagy 3. Autophagy inducers and inhibitors 4. Dual role of autophagy in OS chemoresistance 5. Autophagy and metastasis 6. Autophagy and immunotherapy 7. Autophagy as a prognostic marker in OS 8. Conclusion