The dysregulation of miR‐532‐5p is involved in the development of several cancers. Nevertheless, the roles of miR‐532‐5p in osteosarcoma (OS) have yet to be illuminated. In the present study, we found that miR‐532‐5p was significantly downregulated in both OS tissues and cell lines. The low level of miR‐532‐5p was associated with advance clinical stage and poor overall survival in patient with OS. The functional experiments implied that upregulation of miR‐532‐5p restrained OS U2OS cell growth and metastatic ability in vitro; induced apoptosis, and impaired OS cell growth in vivo. Mechanistically, chemokine (C‐X‐C Motif) ligand 2 (CXCL2) was proved as a target gene of miR‐532‐5p. The inhibitory effects of miR‐532‐5p on OS cell were rescued by CXCL2 overexpression. Altogether, we demonstrated that miR‐532‐5p exerted tumor‐inhibitory functions in OS cell via regulating CXCL2.