Abstract: OBJECTIVE To explore the correlation between Clostridium difficile infection and colorectal cancer and colorectal adenoma. METHODS Totally 354 patients with colorectal adenoma who were treated in the Second Affiliated Hospital of Wenzhou Medical University from Sep 2015 to May 2018 were chosen as the colorectal adenoma group, 257 patients who had colorectal cancer were assigned as the colorectal cancer group, and 60 people who received physical examination were set as the control group. The positive rate of C. difficile infection and toxin genes in the three groups of study objects were recorded and observed. Multivariate logistic model was established to analyze the variables with statistical significance. RESULTS The constituent ratio of family history of colorectal cancer was 3.39% in the colorectal adenoma group, 7.00% in the colorectal cancer group, 0 in the control group, and there was significant difference among the three groups (P<0.05). The incidence rate of C. difficile infection was 12.06% the colorectal cancer group, significantly higher than 4.80% in the colorectal adenoma group, the incidence rate of C. difficile infection of the colorectal adenoma group was significantly higher than that of the control group (P<0.05). The detection rate of toxin A gene (+) toxin B gene (+) was 90.32% in the colorectal cancer group, significantly higher than that in the colorectal adenoma group; the detection rate of binary toxin A gene (+) binary toxin B gene (+) was 6.45% in the colorectal cancer group, significantly higher than that in the colorectal adenoma group (P<0.05). The logistic analysis indicated that the C. difficile infection was the high risk factor for the colorectal adenoma and progression to colorectal cancer. CONCLUSION The C. difficile infection is associated with the colorectal adenoma and colorectal cancer, which may be related to the damage and destruction of effector mechanism due to the toxin A gene, toxin B gene and binary toxin's acting on intestinal mucosal epithelial cells. The C. difficile infection plays a key role in the occurrence and development of colorectal cancer.