CRKL, as a "switch" factor on several oncogenic pathways, plays vital roles in multiple cancers. However, little is known about CRKL in gastrointestinal cancers. Here, we showed that CRKL is involved in colon cancer, which is the most common form of cancer of the digestive system. Immunohistochemistry analysis showed that CRKL expression in colon tumor tissue is significantly higher than normal tissue and CRKL level is associated with tumor differentiation. Suppression of CRKL in colon cancer cells inhibited cell proliferation, migration and invasion, while induced apoptosis. Colon cancer cells xenografts in nude mice showed that CRKL promoted tumorigenesis. Our results suggest that CRKL has the ability to regulate colon cancer malignancy and CRKL has the potential to serve as a diagnosis and prognosis marker and a therapy target of colon cancer.