The purpose of the present study was to detect the expression levels of circulating miR-148a in the peripheral blood of osteosarcoma patients and to further investigate the clinicopathological, diagnostic, and prognostic value of miR-148a. Eighty-nine patients with initially diagnosed osteosarcoma who successfully underwent surgical resection were enrolled in this prospective study. The expression levels of circulating miR-148a were detected by real-time quantitative RT-PCR. All statistical analyses were performed with SPSS 18.0 statistical software to determine the potential values of circulating miR-148a on the clinicopathological factors, diagnosis, and prognosis. The expression levels of circulating miR-148a in osteosarcoma patients were significantly higher than that in the healthy controls (P < 0.001), and miR-148a was capable of distinguishing osteosarcoma patients from healthy controls effectively (AUC = 0.783). In addition, miR-148a expression was significantly associated with tumor size (P = 0.049) and distant metastasis (P = 0.004). Univariate survival analysis demonstrated that patients with miR-148a high expression had significantly poor overall survival (P < 0.001) and disease-specific survival (P < 0.001) after 5 years' operation. Multivariate survival analysis confirmed that miR-148a high expression was an independent predictor for unfavorable overall survival (P = 0.003) and disease-specific survival (P = 0.008), respectively. Our findings demonstrated that detection of circulating miR-148a expression in the peripheral blood have clinical potentials as an indicator of progressive phenotype, a novel diagnostic biomarker and a promising predictor to identify individuals with poor prognosis for osteosarcoma patients.