Metastasis is the principal cause of cancer death and occurs through multiple, complex processes. Epithelial to mesenchymal transition (EMT) is an important process during embryonic development and has also been hypothesized to exhibit a significant role in cancer cell invasion and metastasis. MicroRNAs (miRNAs) are a class of widespread noncoding RNAs. In recent years, many studies have shown that miRNAs could influence the signaling pathways and downstream events that define EMT on a molecular level. However, the exact role and mechanisms of miR-145 in EMT of osteosarcoma (OS) was unknown. In the present study, miR-145 was downregulated in OS tissues and cell lines and it was shown that miR-145 expression was closely correlated with advanced tumor progression in patients of OS. In addition, miR-145 upregulation by miR-145 agomir significantly inhibited MG63 cells invasion and migration ability. MiR-145 was reported to be able to inhibit EMT in cancers. Following the examination of changes in cell epithelial and mesenchymal markers, it was found that upregulation of miR-145 strongly reversed EMT in MG63 cells. Meanwhile, the expression of Snail, a strong E-cadherin transcription repressor was also attenuated by miR-145 agomir. Furthermore, the decreased EMT and invasion and metastasis caused by miR-145 agomir could be restored by Snail siRNA. In conclusion, the results demonstrated that miR-145 could mediate EMT by targeting Snail and miR-145 might be a novel EMT regulating transcription factor that involved in the progression of OS. The specific drugs targeting miR-145-mediated EMT process might be new promising cancer therapies.