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BACKGROUND Colorectal cancer (CRC) is the third most common cancer world-wide. Current treatments, including surgery, radiotherapy, and chemotherapy, are limited by severe side effects and the development of resistance. OBJECTIVE Therefore, it is important to find additional therapies to combat the problem. Gin-senoside Rb1 is the main active ingredient of ginseng, which is a well-known herb in traditional Chinese medicine. Ginsenoside is reported to play an important role in the prevention and treatment of cancer. METHODS We established Azoxymethane (AOM)/Dextran sodium sulfate (DSS) colon cancer model based on inflammation, observed the beneficial effect of ginsenoside Rb1, and detected the changes in gut microbiota. RESULTS Our experimental results showed that gin-senoside Rb1 significantly reduced the levels of TNF-α, IL-6, IL-17A, IL-33, IL-1β, and IL-22, increased the level of IL-10, and also changed the gut microbiota composition. These results suggested that ginsenoside Rb1 can be used to prevent inflammation-associated CRC development and may provide an effective thera-peutic strategy for CRC by relieving chronic inflammation and restoring the gut microenvironment in the AOM/DSS-induced model of colitis-associated colorec-tal cancer in mice. CONCLUSION Ginsenoside Rb1 significantly attenuated AOM/DSS-induced colon carcinogenesis.