A 57-year-old man who had brown urine, jaundice and appetite loss from June 2006 was diagnosed with advanced pancreatic cancer. He received pylorus-preserving pancreatoduodenectomy in July 2006. Liver metastasis in S6 lesion was revealed by abdomen CT and SPIO-MRI in November and December 2006, respectively. Chemotherapy with gemcitabine hydrochloride (GEM) 1,400 mg/body was administered once a week on days 1, 8 and 15 for 4 weeks. At the beginning of this chemotherapy, it seemed to be a stable disease, but abdominal CT revealed a tumor progress in April 2007. So we selected combination chemotherapy with GEM and S-1 as second-line. At first serum CA19-9 was decreased but gradually increased, and the CT scan revealed the tumor progression in the liver and the local recurrence appeared in February 2008. So we selected combination chemotherapy with GEM and nedaplatin as third-line. After 2 months, CT scan revealed no change in tumor size. This combination chemotherapy can be effective in some patients with GEM-refractory pancreatic cancer.