Capecitabine is a prodrug of a 5-fluorouracil (5-FU) that is converted to 5-FU inside the tumor cells. Here, we report a case of 5-FU induced encephalopathy which was subsequently treated with capecitabine without any neurologic complication. A 76-year-old man with rectal adenocarcinoma received chemotherapy, which consisted of 5-FU, leucovorin and oxaliplatin after resection of the primary and metastatic masses. Confusion and agitation were observed during the 2nd cycle of chemotherapy and reappeared during 4th cycle. Both events were completely disappeared within a few days. Capecitabine was administered for 4 cycles without any neurologic toxicity. Capecitabine could be an alternative in patients experiencing 5-FU induced encephalopathy.