There is a liver damage in a serious side effect of regorafenib. Case 1 was a 54-year-old woman, and she had an operation of rectal cancer and metastasized to multiple organs afterwards and started regorafenib as third-line. Erythema exudativum multiform developed on the 8th day after a start and regorafenib was canceled once and reduced on the 21st day when a skin symptom was relieved and restarted. However, because a significant rise of AST, ALT, T -Bil was recognized afterwards, regorafenib was canceled on the 27th day and enforced steroid pulse therapy and was relieved afterwards. Case 2 was a 61-year-old woman, and she had an operation of ascending colon cancer, ovarian metastasis and peritoneum dissemination. Regorafenib was started by frequent occurrence lung metastasis, cancerous pleurisy afterwards as fifth-line. Dissemination erythema developed on the 16th day and a liver damage developed on the 22nd day. Because a rise of AST, ALT went and was prolonged, liver biopsy was enforced in a cause close inspection purpose on the 45th day. A medicamentosus liver damage was diagnosed. The liver enzyme decreased afterwards. It may be easy to make the liver damage by regorafenib serious, and attention is necessary.