To investigate the mechanism of HMGB3 knockdown-mediated colorectal cancer inhibition, we detected a downregulation of N-cadherin, Vimentin and β-catenin proteins after knockdown of HMGB3, and overexpression of HMGB3, we detected a downregulation of N-cadherin, Vimentin and β-catenin proteins were upregulated. This evidence concerns the gene HMGB3 and colorectal cancer.