Colorectal cancer (CRC) is a significant health issue worldwide. Recent studies highlight the critical role of miRNAs in CRC development, particularly miR‐137, which acts as a key tumor suppressor. Despite its known role, further exploration of miR‐137's downstream signaling is needed to understand its biology and therapeutic potential. We examined the methylation status of miR‐137 using one TCGA data and three GEO data sets. A clinical validation cohort of 78 samples was analyzed using MSP for miR‐137 promoter methylation. Various in vitro molecular/cellular and animal experiments were conducted to elucidate miR‐137's role in CRC. Bioinformatic analysis indicated frequent methylation of miR‐137 in CRC tissues, correlating with suppressed expression. EZH2‐mediated H3K27 trimethylation silences miR‐137 in CRC cells by increasing chromatin compaction, reversible by EZH2 siRNA or inhibitor GSK343. miR‐137 inhibits CRC cell proliferation, migration, invasion, and xenograft tumor growth, confirming its tumor‐suppressive role. Using the miRWalk repository showed that miR‐137 regulates the Wnt signaling pathway by reducing typical protein expression in HCT116 and SW480 cells. miR‐137 directly targets RNF4, leading to its downregulation at transcriptional and protein levels, with an observed inverse correlation in CRC tissues. miR‐137 accelerates c‐Myc and β‐catenin degradation by inhibiting RNF4, impacting protein stability and Wnt pathway inhibition. miR‐137 is epigenetically silenced through DNA methylation and EZH2‐mediated H3K27 trimethylation. It regulates the Wnt signaling pathway by targeting RNF4, leading to c‐Myc and β‐catenin destabilization. Restoring miR‐137 or inhibiting RNF4 suppresses CRC cell proliferation, migration, invasion, and tumor growth, highlighting its therapeutic potential in CRC.