A 78-year-old man who developed metastatic liver and lung cancer after undergoing surgery for rectal and sigmoid colon cancer was treated with TAS-102 as fourth-line chemotherapy. He developed high fever and dyspnea and was referred to the emergency room 16 days after receiving the first course of TAS-102. Chest X-ray and computed tomography examinations showed bacterial pneumonia. He was treated with tazobactam/piperacillin, but developed severe dyspnea 4 days later. A diffuse ground-glass appearance was observed in both the lungs on chest X-ray examination, and drug-induced interstitial pneumonitis was suspected. Oxygenation and respiratory support were immediately administered, and steroid pulse therapy with methylprednisolone at 1,000mg/day was initiated. His symptoms and radiographic findings dramatically improved. The TAS102-J003 trial, a double-blind phase 2 trial, showed that interstitial pneumonitis occurs at a rate of only 0.9%, but can lead to severe complications, as observed in the present case. The possibility of interstitial pneumonitis should always be considered when a patient develops a fever and respiratory disorder during treatment containing TAS-102.