The present study was the first to reveal that miR‐125a can decrease the Smurf1 mRNA and protein expression levels in colon cancer cells by directly targeting the 3′‐UTR of Smurf1, which suggests that Smurf1 is a potent target of miR‐125a for CRC prevention and treatment. This evidence concerns the gene SMURF1 and colonic neoplasm.