A 49-year-old man was admitted to the hospital for the upper abdominal pain and was diagnosed as unresectable pancreatic head cancer because of the invasion around the superior mesenteric artery. He was treated with radiochemotherapy, followed by systemic gemcitabine alone for 3 courses. He was further treated with systemic gemcitabine plus S-1 combination therapy for 5 courses. CT examination after these treatments showed a dramatic reduction of the tumor at the head of the pancreas and a pancreatoduodenectomy was performed. Pathologically, there was no residual malignant tumor. He has had no recurrent tumor up until now. Several studies of gemcitabine plus S-1 combination therapy show higher response rates for unresectable tumors. The current case indicates the effectiveness of the radiochemotherapy and gemcitabine plus S-1 combination therapy for locally advanced pancreatic head cancer as a neoadjuvant setting. We consider that multidisciplinary treatment including gemcitabine plus S-1 therapy may prolong the survival time by curative operation.