Background: Osteosarcoma (OS) is a quite malignant bone cancer. However, how long noncoding RNA (lncRNA) regulates OS progression remains poorly investigated. The present study aims to illustrate the potential functions of lncRNA MYOSLID in the regulation of OS progression. Methods: The expression of YOSLID, miR-1286 and RAB13 was analyzed by qRT-PCR. Cell proliferation was determined via CCK8 and colony formation assays. Transwell assay was used to examine migration and invasion. The luciferase reporter assay, RNA pulldown and RNA immunoprecipitation (RIP) assays were utilized to detect the interactions among MYOSLID, miR-1286 and RAB13. Results: The expression of MYOSLID was upregulated in OS tissues and cell lines. MYOSLID overexpression predicted poor prognosis in OS patients. MYOSLID knockdown suppressed proliferation, migration and invasion of OS cells. MYOSLID was the sponge for miR-1286 and inhibited its expression while miR-1286 targeted RAB13 directly. MYOSLID promoted RAB13 expression via sponging miR-1286. Conclusion: Our work demonstrated that the MYOSLID/miR-1286/RAB13 axis is a novel regulatory signaling in promoting OS progression.