OBJECTIVE:The aim of this study was to investigate the serum level of microRNA (miR)-21 in patients with osteosarcoma and its correlation with chemosensitivity and prognosis. METHODS: miR-21 levels in sera from 65 patients with osteosarcoma and 30 healthy controls were measured by real-time reverse transcription-polymerase chain reaction. Correlations between serum miR-21 and clinicopathological features in patients with osteosarcoma were determined. The prognostic significance of serum miR-21 was assessed using a Cox proportional hazards model. RESULTS: The serum level of miR-21 was significantly higher in patients with osteosarcoma than in control subjects. High serum miR-21 was significantly correlated with advanced Enneking stage and chemotherapeutic resistance. Univariate and multivariate analyses for overall survival showed that upregulation of serum miR-21 was an independent, unfavourable prognostic factor for patients with osteosarcoma (hazard ratio, 2.325). CONCLUSIONS: miR-21 might be a good candidate for a therapeutic target, and a potential biomarker for the prediction of chemotherapeutic sensitivity and prognosis in patients with osteosarcoma.