We report a case of effective S-1 plus oxaliplatin (SOX) treatment for duodenal cancer with liver metastases. The patient was a 70-year-old female diagnosed with duodenal carcinoma that was unresectable because of liver metastasis(cT4N1M1, cStage IV in UICC 7th). She received SOX treatment(100mg/m / 2 of oxaliplatin on day 1 combined with 40 mg/day of S-1 twice daily on days 1-14, was repeated every 3 weeks). After 4 courses, a partial response was confirmed by computed tomography and no severe adverse events were observed. However, during the 5th courses, several new liver metastases were observed, so we changed to weekly paclitaxel treatment. This case suggests that SOX treatment may be an effective chemotherapy for advanced primary duodenal carcinoma.