Dysregulation of microRNA (miRNA) has been observed in several types of tumors, including osteosarcoma. Biochip analysis was used to identify miRNAs differentially expressed in osteosarcoma tissues. The targeting sites of miR-627-3p were analyzed using miRDB software and fluorescein reporter gene. MTT and Transwell assays were used to analyze the effects of miR-627-3p on the growth and migration of osteosarcoma cells. Western blotting and real-time PCR were used to detect the effects of miR-627-3p on related proteins. In vivo experiments were conducted to verify the effect of miR-627-3p on osteosarcoma. We focused on miR-627-3p because it was the most significantly downregulated miRNA in our screening study. Through luciferase reporter assays, western blotting and real-time PCR we found that miR-627-3p directly targets PTN, and that expression levels of miR-627-3p and PTN are negatively correlated in osteosarcoma cells. Downregulation of miR-627-3p promoted osteosarcoma cell proliferation and metastasis, while its overexpression had the opposite effect. By targeting PTN, miR-627-3p also suppressed expression of Cyclin D1 and MMP2. MiR-627-3p inhibited osteosarcoma metastasis in vivo. Thus, miR-627-3p may be a useful therapeutic target for the treatment osteosarcoma or prevention of metastasis.