Objective: To study the carcinogenic effects of Claudin-7 gene knockdown on the liver metastasis of colon cancer (LMCC) nude mice model(NMM) and its preclinical research. Methods: After 60 days of the spleen injection, HT29 colon cancer cells transfected by recombinant clone vector pcDNA6-Claudin-7 gene knockdown were used to establish the LMCC-NMM. The tumor bearing nude mice were randomized into 2 groups, Claudin-7 knockdown group and Scramble control group. In addition, Claudin-7 knockdown group was cancer cells injected into spleen to study group and control group, evaluating metastatic tumor formation, liver metastasis tissues were investigated expression of Claudin-7 protein via immunohistochemistry. Results: The liver weight, liver metastasis scores, lymph node metastasis rate, bloody ascites rate, peritoneal seeding rate, and distant metastasis rate of Claudin-7 knockdown group were significantly greater than that in the control group (p<0.05). Expression of Claudin-7 protein was marked histopathological difference of liver metastasis tissues between Claudin-7 knockdown group and control group,and difference was statistical y significant (p<0.05). Live tables showed that Claudin-7 knockdown group is inversely correlated with cumulative survival of LMCC-NMM (p<0.01). Conclusion: Claudin-7 gene knockdown may be promote the formation of LMCC-NMM, and expression of Claudin-7 as an evaluating index for tumor metastasis.