To investigate the effects of polysaccharopeptide (PSP) of Trametes versicolor on colorectal cancer-associated pathogenic enterobacteria (CAPEB), male mice were randomly divided into three groups: wild type group, Model group and PSP group. The mice in Model and PSP group were intraperitoneally injected with azoxymethane (AOM) and administrated with three cycles of dextran sodium sulfate (DSS) in drinking water to induce colorectal cancer. Mice in the PSP group were administrated daily with PSP (650 mg/kg) by gavage for 13 weeks. Diseases active indexes (DAI) were scored during the three DSS cycles, and the relative abundances of bacteria in stool samples were determined by quantitative real-time polymerase chain reaction. The results showed that the DAI of the PSP group was significantly decreased in the first two rounds of DSS treatment (P<0.05, P<0.01) compared to the model group. The relative abundances of each potential CAPEB of the PSP group, in terms of P. anaerobius, A. muciniphila, B. fragilis and C. symbiosum, were all lower than those of the model group, and the abundance of the first three bacteria mentioned above was significantly decreased in the mid-term of the experiment (P<0.05, P<0.01, P<0.05). These results indicated that PSP could alleviate DSS-induced inflammation and down-regulate abundance of colorectal cancer-associated pathogenic enterobacteria in mice, suggesting that PSP may have a preventive effect on inflammation-associated colorectal cancer.