In May 2006, a 79-year-old man underwent left colectomy and D2 lymphadenectomy for descending colon cancer (fStage II , Cur A). No adjuvant chemotherapy was done. Eighteen months after surgery, the serum tumor marker level was increased (CA19-9 526 U/mL), and multiple liver metastases (H2) and peritoneal dissemination were detected using abdominal CT. He was treated with S-1 plus CPT-11 therapy, because mFOLFOX6 as a standard chemotherapy for advanced colorectal cancer was rejected. After 4 courses, tumor markers normalized and abdominal CT revealed a partial response. At present, progression-free survival (PFS) is 240 days. In our case, this regimen was found to be convenient and safe in an outpatient compared with FOLFIRI and FOLFOX. This case suggested that S-1 plus CPT-11 therapy could well be a promising systemic chemotherapy for patients with advanced colorectal cancer.