Emerging evidence indicates that microRNAs (miRNAs) are often aberrantly expressed in human cancers. Meanwhile, the importance of miRNAs in regulating multiple cellular biological processes has been appreciated. The aim of this study was to investigate the significance of miR-455 and identify its possible mechanism in regulating colorectal cancer (CRC) progression. We found that the expression of miR-455 was sharply reduced in CRC tissues and cell lines. Importantly, the low expression of miR-455 was associated with poor overall survival of CRC patients. Overexpression of miR-455 in CRC cell lines significantly inhibited cell proliferation and migration in vitro. Moreover, GATA-binding protein 6 (GATA6), whose expression can be inversely regulated by miR-455 in CRC cell lines, was validated as a direct target of miR-455. Overall, our results revealed that miR-455 functions as a tumor suppressor, and its downregulation may contribute to CRC progression. Our study may provide a novel therapeutic target for CRC in the future.