Osteosarcoma is the most common type of primary malignant bone tumor, and deregulated microRNAs (miRNAs or miRs) in osteosarcoma have attracted great attention. In the present study, through miRNA microarray analysis, it was identified that miR-148a expression was significantly increased in osteosarcoma tissues. Increased miR-148a expression was significantly correlated with tumor progression and prognosis. Furthermore, increased miR-148a expression could promote osteosarcoma growth in vitro and in vivo, and the tumor-promoting effect was due to enhanced activation of the phosphoinositide 3-kinase signaling pathway caused by miR-148a-mediated inhibition of phosphatase and tensin homolog expression. Together, the present results suggest a role for miR-148a in osteosarcoma development and its potential use in prognosis prediction and cancer therapy.