microRNAs (miRNAs) are small, noncoding RNAs that are involved in many biological processes, and aberrant regulation of miRNAs is always associated with cancer progression and development. Abnormal expression of miRNA-132 (miR-132) has been found in some types of cancer, but the effects and potential mechanisms of miR-132 in colorectal cancer (CRC) have not been explored to date. In this study, quantitative real-time polymerase chain reaction was used to investigate the level of miR-132 in CRC tissues and their paired adjacent normal tissues. Bioinformatics analysis indicated that the mechanism underlying the tumor suppressor role of miR-132 in CRC cells may play a role in tumor suppression by targeting paxillin. Furthermore, methylation-specific polymerase chain reaction was performed to evaluate the methylation status of the miR-132 regulatory region. A DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, was used to activate the expression of miR-132 in CRC cells in vitro. Downregulation of miR-132 may occur as a result of hypermethylation and implies a poor prognosis in CRC; therefore, triggering miR-132 reexpression by using DNA methyltransferase inhibitors may be a potential molecular therapeutic target for CRC.