MicroRNA-452 (miR-452) is dysregulated in some human malignancies, and is correlated with tumor progression. However, its expression and function in human colorectal cancer (CRC) remain unclear. The aim of our study was to explore the effects of miR-452 in CRC tumorigenesis and development. Using reverse transcription quantitative real-time polymerase chain reaction, we detected miR-452 expression in CRC cell lines and primary tumor tissues. We also examined the association between miR-452 expression and clinicopathological factors. We then investigated the effects of miR-452 on the biological behavior of CRC cells. miR-452 expression was significantly downregulated in CRC compared with the adjacent noncancerous tissues. A low level of miR-452 was associated with larger tumor size, deeper invasion depth, and advanced TNM stage. Multivariate Cox regression analysis identified decreased miR-452 expression as an independent factor predicting poor prognosis for CRC patients. In addition, in vitro functional analysis showed that overexpression of miR-452 in HCT116 cells reduced cell proliferation, promoted cell apoptosis, and inhibited cell invasion and migration. These findings indicate that miR-452acts as a tumor suppressor in CRC, and would serve as a novel molecular therapeutic agent for the treatment of the disease.