Objective: To investigate the effect of CDX2 gene expression on growth of colon cancer cells. Methods: Human colon cancer HT29 and SW480 cells transfected with lentiviral vectors expressing CDX2-shRNA, or empty lentiviral vectors or without any transfection were transplanted subcutaneously into nude mice to generate tumor xenografts, respectively. Then the growth of the xenografts in the three groups of mice was observed. At 28 d after transplantation, the mice were sacrificed and their xenografts were isolated and weighed, and the expressions of Ki-67 and CDX2 were determined by immunochemical staining and Western blot, respectively. Results: In either interference group (transplantation of HT29 or SW480 cells transfected with lentiviral vectors expressing CDX2-shRNA) compared with corresponding blank control (transplantation of HT29 or SW480 cells without any transfection), the tumor growth speed was significantly enhanced, the tumor weight was significantly elevated (SW480: 679.11 mg vs. 379.36 mg; HT29: 715.78 mg vs. 427.07 mg) and the Ki-67 protein expression was significantly increased, while the CDX2 protein expression was significantly upregulated in the tumor tissue (all P<0.05). No significant difference was found in any of above parameters between the two negative control groups (transplantation of HT29 or SW480 cells transfected with empty lentiviral vectors) and their blank control groups (all P>0.05). Conclusion: Inhibition of CDX2 gene expression can promote the growth of human colon cancer cells in nude mice, so CDX2 is probably an important cancer suppressor gene.