Abstract: Objective The incidence rate of diarrhea in patients with malignant tumor is high. The Clostridium difficile infection is an important cause. However, it is difficult to distinguish clinically. This study intended to investigate the clinical characteristics for Clostridium difficile-associated diarrhea among cancer patients in China. Methods We investigated the prospective clinical database for cancer patients combined with diarrhea, and a total of 472 patients included in this study, who were divided into 2 groups depending on whether or not Clostridium difficile infection:Clostridium difficile infection group (Group A, n=95) and Non-Clostridium difficile infection group (Group B, n=377). Polymerase chain reaction (PCR) was used to detect the Clostridium difficile poisonA (tcdA) and Clostridium difficile poison B (tcdB). The patient general information was recorded, blood routine examination and biochemical test were performed. The ECOG score was recorded before chemotherapy and during diarrhea. The side effects, chemoradiotherapy, proton pump inhibitor and antibiotic therapy within 4 weeks before diarrhea, the time of antibiotic therapy were also recorded. Propensity score matching analysis with preset caliper width 0.1 was used to keep the equilibrium in general information between groups, and the two groups were matched with 1:1. The general information and malignant tumor treatment information of the patients were recorded. Results A total of 91 matched pairs were selected from the patients after the propensity score matching analysis, and no difference was found in general information between Group A and Group B (P>0.05). Compared with Group B, the level of plasma albumin decreased in Group A (P<0.01), the proportion of antibiotic application, proton pump inhibitor, positive fecal occult blood test and ECOG score after chemotherapy were increased in Group A (P<0.05 or P<0.01). No difference was found in side effects between two groups. Conclusion The level of plasma albumin decreased and the incidence of positive fecal occult blood test increased in patients with malignant tumor associated diarrhea of Clostridium difficile infection. The use of antibiotics, chemotherapy and proton pump inhibitors may increase the risk of Clostridium difficile infection in patients with malignant tumors.