Objective To investigate the expression of B-cell translocation gene 1 (BTG1) in ulcerative colitis (UC) and colitisassociated colorectal cancer (CAC), and whether it affects the“ inflammation-cancer” transformation process by regulating epithelialmesenchymal transition (EMT). Methods Clinical intestinal mucosal tissue samples were collected and the expression level of BTG1 and EMT markers were detected. Using HCT116 cells, an intervention experiment on BTG1 knockdown and overexpression was conducted to analyze the changes in EMT-related protein expression and the alterations in cell migration and invasion abilities. In addition, an azoxymethane (AOM)/ (dextran sulfate sodium (DSS) mouse CAC model was established to compare colitis and tumor burden in wild-type and intestinal epithelial-specific BTG1 overexpressing mice. Results BTG1 showed a progressive decrease in the active phase of UC and in the CAC tissues. Its expression level was negatively correlated with the disease activity, and was accompanied by the loss of E-cadherin and the increase in Vimentin expression. At the same time, the results of in vitro experiments confirmed that BTG1 knockdown could induce EMT in cells and enhance their migration and invasion abilities, while overexpression of BTG1 reversed this phenotype. The in vivo experiments demonstrated that overexpression of BTG1 could significantly alleviate the inflammatory response in the colon, reduce the number of tumors, shrink the tumor diameter, and also improve the expression levels of intestinal barrierrelated proteins. Conclusion BTG1 is lowly expressed during the progression from UC to CAC. Its downregulation promotes inflammation-cancer transformation via activating the EMT process. Restoring BTG1 expression can inhibit the EMT process, alleviate inflammation and reduce tumor burden, indicating that BTG1 may serve as a potential therapeutic target for this disease.