A 90-year-old female complaining of severe upper abdominal pain was transferred to our institution. The patient had been prescribed with calcium polystyrene sulfonate (CPS) for the treatment of hyperkalemia following myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) associated glomerulonephritis. Physical examination revealed diffuse tenderness over the abdomen, with signs of peritoneal irritation. Abdominal computed tomography (CT) revealed the retention of ascites, free air in the abdominal cavity, and the retention of hard stools in the left-sided colon. The diagnosis of intestinal perforation was immediately confirmed; thereafter, the patient underwent emergency surgical treatment. Surgical findings revealed a perforated site in the descending colon surrounded with hard stools. Histopathology of the perforated colon revealed crystalline materials, suggestive of association with CPS. CPS is a cation-exchange resin used to treat hyperkalemia; the major adverse effect in patients receiving CPS is constipation. When CPS is administered to patients with frequent constipation or the elderly, the risk of intestinal perforation should be considered.