Objective To retrospectively observe and compare the efficacy and safty of irinotecan or oxaliplatin combined with fluoropyrimidine in the first line treatment of advanced gastric cancer. Methods 71 patients were divided into two groups. The irinotecan group consisted of 37 patients. Irinotecan 180 mg/m2 was injected in 90 minutes on d1. And the oxaliplatin group consisted of 34 patients. Oxaliplatin 85 mg/m2 was injected on d1. All the groups combined fluoropyrimidine. 5-Fluorouracil (5-Fu) 400 mg/m2 and leucovorin 200 mg/m2 were injected on d1,2 and 5-Fu 600 mg/m2 was 22 h continuous injected on d1,2, every 2 weeks was a cycle. It could also take capecitabine 1.0 g/m2 or tegafur-gimeracil-oteracil potassium 25 mg/m2 Bid for d1~14 orally, every 3 weeks was a treatment. Results 65 patients were evaluated. The response rates were 32.35% and 22.58%, the disease con-trol rates were 76.47% and 70.97%, and the median progression free survival (PFS) were 5 (3.962~6.038) months and 4 (2.730~5.270) months in irinotecan group and oxaliplatingroup, respectively, with no significant difference (P>0.05). Toxicity was tolerable, major adverse events were neutropenia, nausea and vomiting in two group. The incidence rate of diarrhea (45.95%) was higher in irinotecan group, and the peripheral nerve toxicity was 29. 41% in oxaliplatin group. Conclusion The effects of irinotecan or oxaliplatin combined with fluoropyrimi-dine in the treatment of advanced gastric cancer are comparable, and their toxicities are tolerable.