Objective: To investigate microRNA-451 (miR-451) expression in colorectal cancer (CRC) tissues and its clinical significance. Methods: The miR-451 expression in tumor tissues and normal mucosa samples obtained from 40 CRC patients, as well as 8 different CRC cell lines were examined by real-time quantitative reverse transcription-PCR (RT-qPCR). The relations of miR-451 expression with clinicopathologic profiles of CRC were analyzed. Results: Compared with normal mucosal tissues, miR-451 expression level was significantly reduced in either CRC tissues or all the CRC cell lines (all P<0.05). Comparison between groups divided by clinicopathologic profiles showed that the miR-451 expression difference was associated with the histologic classification and degree of differentiation of the tumor, and its expression level was lowest in mucinous adenocarcinoma and poorly differentiated adenocarcinoma (both P<0.05). Conclusion: The miR-451 expression in CRC tissues is generally decreased, and the decreasing degree is related to the histologic classification and differentiation of the tumor.