Cell proliferation assay and flow cytometry analysis revealed that the overexpression of CELF6 induced G1 phase arrest, depletion of CELF6 promoted G1/S transition and cancer cell proliferation, overexpression of p21 reversed the effect of CELF6 siRNA on cell proliferation, indicating that CELF6 is a potent tumor suppressor in colorectal cancer, the inhibitory effect of CELF6 is likely mediated through p21. Here, CELF6 is linked to colorectal cancer.