Objective: To investigate the expressions of miRNA-21, miRNA-135b and miRNA-141 in colon cancer and their significance. Methods: The expressions of the three miRNAs in colon cancer tissues and their adjacent normal colonic mucosal tissues, as well as in the plasma of colon cancer patients and healthy controls were determined by fluorescent real-time quantitative PCR. The relations of the three miRNAs with clinicopathologic factors of colon cancer patients were analyzed. Results: The expression levels of the three miRNAs in colon cancer tissue were all significantly higher than those in adjacent colonic mucosal tissue, and in plasma of colon cancer patients were all significantly higher than those in plasma of healthy controls (all P<0.05). In colon cancer patients, the miR-21 expression level was significantly related to TNM stage and invasion depth, the miR-135b expression level was significantly associated with TNM stage and lymph node metastasis, and the miR-141 expression level was significantly linked to TNM stage, invasion depth and lymph node metastasis (all P<0.05). The miRNA21 showed no obvious correlation between its expression level in colon cancer tissue and plasma of the colon cancer patients (r=0.459, P=0.072), but either miRNA135b or miRNA-141 had a positive correlation between its expression level in colon cancer tissue and plasma of the colon cancer patients (r=0.686, P=0.042; r=0.742, P=0.026). Conclusion: The expressions of miRNA-21, miRNA-135b and miRNA-141 are all up-regulated in colon cancer patients, and they may be closely related to the recurrence and development of this cancer, as well as could be potential tumor markers or therapeutic targets.