MicroRNA-132 (miR-132), an angiogenic growth factor inducible microRNA in the endothelium, facilitates pathological angiogenesis. Previous study showed that miR-132 was downregulated in human osteosarcoma. However, its functional attributes associated with tumor progression of osteosarcoma have not been fully elucidated. The aim of this study was to investigate the clinical significance of miR-132 expression in human osteosarcoma. miR-132 expression was detected by quantitative reverse transcription polymerase chain reaction using 166 pairs of osteosarcoma and noncancerous bone tissues. Then, the association of miR-132 expression with clinicopathological factors or survival of osteosarcoma patients was also evaluated. miR-132 expression was significantly lower in osteosarcoma tissues than that in corresponding noncancerous bone tissues (P < 0.001). In addition, miR-132 expression was decreased in the osteosarcoma specimens with advanced clinical stage (P = 0.009), positive distant metastasis (P = 0.006), and poor response to chemotherapy (P = 0.009). Moreover, both the univariate and multivariate analyses showed that osteosarcoma patients with low miR-132 expression had poorer overall and disease-free survival (both P < 0.001), and low miR-132 expression was an independent prognostic factor for both overall (P = 0.001) and disease-free survival (P = 0.006). These findings offer the convinced evidence for the first time that miR-132 may participate in tumor progression of osteosarcoma and loss of miR-132 expression may be a predictor for unfavorable outcome of osteosarcoma patients.