ObjectiveTo evaluate the expression of miR-338-5p in colorectal cancer tissues and study its role in colon cancer cell proliferation, apoptosis, and cell cycle. MethodsThe expression of miR-338-5p was detected by real-time PCR in the colorectal cancer tissues and corresponding adjacent to cancer tissue samples. The miR-338-5p-mimics was transfected into the colon cancer cell lines HCT116 and SW620 to investigate its role in cell proliferation, apoptosis, and cell cycle. The cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. The cell cycle was also analyzed by flow cytometry. Results①miR-338-5p expression was significantly downregulated in the colorectal cancer tissues as compared with corresponding adjacent to cancer tissue samples(P < 0.01). 2 Compared with the transfected negative control cells, the proliferation ability of colon cancer cell HCT116 or SW620 was significantly decreased(P < 0.01), cell apoptosis was significantly increased[HCT116 cell:(11.43±0.67)% versus(7.98±0.36)%, P < 0.01;SW620 cell:(10.5±0.2)% versus(7.93±0.5)%, P < 0.01), and cell G1 was arrested[HCT116 cell:(80.41±1.34)% versus (64.87±1.83)%, P < 0.01;SW620 cell:(68.76±0.41)% versus(54.89±0.78)%, P < 0.01) after transfecting miR-338-5p-mimics cells. ConclusionmiR-338-5p may act as an anti-oncogene in colorectal cancer through regulation of cell proliferation, apoptosis, and cell cycle.