A 50-year-old man undergoing operations for sigmoid colon cancer, small intestine invasion, and liver metastasis was given adjuvant chemotherapy postoperatively. During the course, lung, brain and bone metastasis were found, FOLFIRI therapy was started. Fifth FOLFIRI therapy was performed, but on the night of the next day, he was transported on an emergency basis to our hospital because of a coma. Laboratory examination revealed hyperammonemia, so aminoleban was started for its treatment. After 3 days in the hospital, consciousness and serum ammonia were improved. Cases of hyperammonemia caused by 5-FU have been reported in the literature, and this case was diagnosed with the same. Hyperammonemia should be taken into account as a differential diagnosis in the disturbance of consciousness in chemotherapy.