Accumulating evidence reveals that miR-449a is expressed at a low level in several tumors and cancer cell lines, and acts as a tumor suppressor in several cancers. However, its role in osteosarcoma (OS) is not well understood. In the present study, we found that miR-449a was significantly downregulated in both OS tissues and cell lines. Furthermore, low expression level of miR-449a was correlated with advanced tumor stage, metastasis, and predicted a poor overall survival in OS patients. Additionally, restoration of miR-449a in OS cell lines U2OS and Saos-2 reduced cell viability, promoted cell apoptosis in vitro, and suppressed tumorigenicity in vivo. Moreover, BCL2, an antiapoptotic molecule, was identified to be a direct target of miR-449a, and the proapoptotic function of miR-449a was mainly through targeting BCL2 expression. Taken together, our results demonstrated a tumor-suppressive role of miR-449a in OS progression and suggested a potential therapeutic target for OS.