Pseudomembranous colitis, an antibiotic-associated diarrhea, needs early diagnosis and treatment for the high fatality rate in severe cases. We report a case of pseudomembranous colitis following the use of antibiotics in febrile neutropenia (FN). A 74-year-old man with non-curative resected sigmoid colon cancer was treated with cefepime in FN induced by chemotherapy. Complications of diarrhea were seen on day 2. Paralytic ileus and disseminated intravascular coagulation were also complications. He was diagnosed as pseudomembranous colitis for Clostridium difficile toxin-positive. Vancomycin enemas were administered because oral administrations were impossible, and the effect was provided. Vancomycin enemas are an effective therapy for patients with severe pseudomembranous colitis unable to tolerate oral medications because of ileus.