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Summary: Inflammatory bowel diseases (IBDs) contribute to the tumorigenesis of colorectal cancer (CRC). Here, we describe a step-by-step protocol for the construction of colitis-associated CRC murine model by sequential utilization of azoxymethane and dextran sulfate sodium. We also detail steps to determine the degree of murine intestinal inflammation and to generate colorectum Swiss roll for further histopathological analyses. This is a convenient and reproducible protocol for colitis-associated CRC murine model by the induction of general chemical reagents.For complete details on the use and execution of this protocol, please refer to Yang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.