Epithelial-to-mesenchymal transition (EMT) plays an essential role in cancer invasion and metastasis and is associated with tumor recurrence in colorectal cancer (CRC). However, the mechanism that contributes to EMT have not been fully understood in CRC. In the present study, we showed that miR-363-3p was frequently down-regulated in CRC tissue specimens with lymph node metastasis. Moreover, we demonstrated that down-regulation of miR-363-3p promoted CRC cell migration and invasion, and induced EMT in vitro and in vivo, revealing that miR-363-3p playes a potential tumor-suppressive role in CRC. Analysis of the underlying mechanisms revealed that miR-363-3p could regulate Sox4 expression by directly targeting its 3'untranslated region. Down-regulation of miR-363-3p increased Sox4 expression and induced EMT, while overexpression of miR-363-3p decreased Sox4 expression. Taken together, our findings indicate that miR-363-3p is involved in CRC metastasis and functions as a tumor suppressor via negatively regulating Sox4. Therefore, the up-regulation of miR-363-3p in human CRC may have therapeutic benefits. (C) 2016 Elsevier Inc. All rights reserved.