Colon perforation can be caused by a variety of entities, including iatrogenic trauma, tumors, ischemia, inflammatory bowel disease, and steroid use. Parasitic infection rarely leads to colon perforation. Secondary peritonitis results from mixed microorganism infection, including enterococci, enteric bacilli, and anaerobes. A combination of an optimal antibiotic regimen and surgical intervention is of paramount importance. Nevertheless, intra-abdominal infections usually have a high mortality rate. Schistosomiasis occurs worldwide. S. japonicum infection is endemic in Asia. The most common complications of gastrointestinal schistosomiasis are periportal fibrosis, intestinal polyposis, and bowel stricture. Rarely, schistosomiasis results in colon perforation. The diagnosis of schistosome infections is based on ova in stool or tissue specimens, and/or immunologic diagnostic tests. The most effective anti-schistosomiasis agent is praziquantel. Herein, we describe an unusual case of colon perforation associated with Schistosoma japonicum infection, which resulted in severe peritonitis and led to the patient's death.