Background: Gemcitabine and S-1 are both effective antitumor chemotherapeutic agents for pancreatic cancer. We evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) as first-line chemotherapy in Chinese patients with metastatic or advanced pancreatic cancer. Methods: Patients with previously untreated metastatic or advanced pancreatic cancer who had measurable lesion(s) were enrolled. Gemcitabine was administered intravenously at a dose of 1,000 mg/m (2) during 30 min on days 1 and 8 and oral S-1 was given twice daily (BSA < 1.25 m(2), 80 mg/day; 1.25 ≤ BSA < 1.50 m(2), 100 mg/day; 1.50 m(2) ≤ BSA, 120 mg/day) on days 1-14 followed by a drug-free interval of 1 week every 21-day cycle. Results: Twenty-five patients were enrolled between 2012 and 2014. The assessed overall response rate was 24 % partial response in 6 patients, 56 % stable disease in 14 patients, and 20 % progressive disease in 5 patients. Sixteen patients (64 %) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.6 months (95 % CI 4.1-6.7 months) and 10.2 months (95 % CI 6.5-14.2 months). The major hematological toxicities were included grade 3/4 leucocytopenia in 8 patients (32 %), grade 3/4 neutropenia in 13 patients (52 %), and one patients (4 %) suffered grade 1 febrile neutropenia. The common grade 3/4 non-hematological toxicity was Anorexia, rash and fatigue, held the proportion of 12%, 16% and 12%, respectively. Conclusions: Gemcitabine and S-1 (GS) combination therapy showed promising activity with acceptable toxicities as first-line chemotherapy in Chinese patients with metastatic or advanced pancreatic cancer.