A 76-year-old woman had underwent 5-fluorouracil(5-FU), oxaliplatin(L-OHP)combination therapy(mFOLFOX6)as first-line chemotherapy for peritoneal recurrence after resection of sigmoid colon cancer. She showed severe general fatigue and disturbance of consciousness on the second day of the 12th course of chemotherapy. Computed tomography of the head detected no abnormal findings in the central nervous system. The laboratory results revealed a marked hyperammonemia. She was diagnosed as a disturbance of consciousness due to hyperammonemia and treated her with branched- chain amino acid solution. Then the disturbance of consciousness resolved on the following day. After changing the regimen of chemotherapy, the disturbance of consciousness was not found. Recently, it has been reported that high-dose 5-FU regimen such as mFOLFOX6 causes hyperammonemia as a rare adverse event. We should take hyperammonemia into account when disturbance of consciousness occurs during high-dose 5-FU chemotherapy.