Objective: To evaluate the efficacy and adverse reactions of the modified DCF regimen for first-line therapy of advanced gastric cancer. Methods: During June 2008 to June 2011, 48 primarily treated patients with advanced gastric cancer underwent the DCF regimen that consisted of docetaxel (75 mg/m2 intravenous drip on day 1), cisplatin (20 mg/m2/day intravenous drip on day 1 to 3), and 5-fluorouracil (750 mg/m2/day continuous intravenous infusion on day 1 to 5). Every 21 d constituted one cycle of treatment, and at least two cycles were required for efficacy evaluation. Results: The deadline of follow-up was February 2013, and no patient was lost to follow-up. In the entire group of patients, the overall response rate (ORR) was 29.2% (14/48) and disease control rate (DCR) was 87.5%, while specifically, complete remission (CR) was achieved in one case (2.1%), partial remission (PR) was obtained in 13 cases (27.1%), stable disease (SD) was seen in 28 cases (58.3%), and disease progression (PD) occurred in 6 cases (12.5%). The median time to progression (TTP) was 6.9 months and median overall survival (OS) was 12.5 months, respectively. The major adverse events were myelosuppression, gastrointestinal reactions and alopecia, and the incidence of granulocytopenia was 66.7% (32/48) with III-IV degree accounting for 21.8 (7/32), and thrombocytopenia was 20.8% (10/48) with III-IV degree; no treatment-related death such as serious infection or bleeding occurred. Post-chemotherapy KPS score was an independent influential indicator for prognosis. Conclusion: Modified DCF regimen for first-line therapy of advanced gastric cancer shows definite efficacy and good tolerance.