Hyperammonemic encephalopathy is a rare side effect of 5-fl uorouracil (5-FU). We present a 58-year-old male with adenocarcinoma of ascending colon who was treated with salvage chemotherapy that consisted of infused 5-FU (2400 mg/ m2) for 46 hours, irinotecan (180 mg/m2) for 90 minutes and bevacizumab (5 mg/kg) for 90 minutes every two weeks. Sudden onset of conscious disturbance developed after completion of the fourth cycle of chemotherapy. He presented to our emergency room with hyperammonemic encephalopathy and acute kidney injury. After fl uid resuscitation and administration of lactulose for 3 days, he recovered well and his renal function became normal. We reduced the dose of 5-FU (1200 mg/m2) in the fi fth cycle of chemotherapy. He completed the fi fth cycle of chemotherapy well without development of hyperammonemia. When patients undergoing chemotherapy comprising 5-FU present with conscious disturbance, hyperammonemia should be considered and acute kidney injury should be prevented.