An extracellular polysaccharide (EPS1-1) extracted from the fermentation broth of Rhizopus nigricans has been proved to enhance the immunity of immunosuppressed mice. The purpose of this study was to investigate the beneficial effects of EPS1-1 on the intestinal immunity of mice with colorectal cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The results showed that EPS1-1 could resist hydrolysis in an artificial stomach. Oral EPS1-1 modulated gut microbiota and increased the concentration of total short-chain fatty acids (SCFAs) in the feces of colorectal cancer mice compared with the AOM/DSS only-treated mice. Furthermore, EPS1-1 increased the villus length, ratio of villus length and crypt depth in colonic tissues, and improved the number of acid mucus-secreting goblet cells in mice with colorectal cancer. These findings suggest that EPS1-1 might play an important role in the improvement of intestinal function in mice with colorectal cancer, which indicate its strong potential as efficient bio-secure immunotherapy for clinical applications or adjuvant drug. •EPS1-1 could modulate gut microbiota to protect intestine of mice with colorectal cancer.•EPS1-1 could increase total SCFAs, villus length and ratio of V/C compared to model group.•EPS1-1 could increase mucus secreting goblet cells in mice with colorectal cancer.