A 66-year-old man with malignant fibrous histiocytoma suffered from severe right arm and shoulder pain. Methadone 45 mg per day was effective in alleviating his pain, but he experienced severe drowsiness following trabectedin induced liver injury. We suspected that impaired methadone metabolism was responsible for the drowsiness. Reduction in methadone dosage and liver supporting therapy was effective in reducing the drowsiness.