Objective: To investigate the expression of miR-21, miR-221, miR-143, and miR-106a in patients’ osteosarcoma samples, and to explore the correlation between these microRNAs (miRNAs) and the clinical stage of osteosarcoma. Methods: RNA was extracted from tumor and tumor-adjacent normal bone tissues from 94 patients with osteosarcoma. RNA reverse-transcription was carried out using an miRNA reverse transcription kit. The levels of miR-21, miR-221, miR-143, and miR-106a in osteosarcoma and normal bone tissues were analyzed by real-time polymerase chain reaction using SYBR Premix Ex Taq™II. Results: The expression levels of miR-21, mirR-221, and miR-106a were significantly higher in 90.42%, 84.04%, and 92.55 % of the osteosarcoma samples compared to the adjacent normal tissues ( P<0.05), respectively. While the expression of miR-143 was significantly lower compared to the adjacent normal tissues ( P <0.05). Moreover, the expression levels of miR-21 and miR-221 were positively correlated with the Enneking clinical stage and the presence of lung metastasis ( P <0.05), while the expression levels of miR-143 and miR-106a showed a significant inverse and direct correlation respectively, with the tumor grade. Conclusions: The upregulation of miR-21, miR-221, and miR-106a, as well as the down-regulation of miR-143 were correlated with the pathological stage, tumor grade, and lung metastasis. Therefore, the levels of these miRNAs can serve as potential biomarkers for the early diagnosis of osteosarcoma, and can be used as potential therapeutic targets.