ObjectiveTo evaluate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and efficacy of fluorouracil-based chemotherapy in patients with advanced gastric cancer (AGC). MethodsComputer retrieval in China Journal Full-text Database, Chinese Science and Technology Periodical Database, Wanfang database, Chinese Biomedical Literature Database, PubMed, EMbase, Cochrane Library and Web of Science Database (from their establishment to May 28, 2013) was performed to include case-control studies on MTHFR gene C677T polymorphism and sensitivity to fluorouracil-based chemotherapy in patients with advanced gastric cancer. Statistical analysis was done by using RevMan 5.1 software. ResultsSeven case-control studies with 775 patients were included. The meta-analysis showed that among MTHFR C677T genotypes, for TT vs. CC, OR=4.63, 95%CI (1.23, 17.4); and for CC+CT vs. TT, OR=0.21, 95%CI (0.06, 0.78). Subgroup analysis of Asian group showed that for TT vs. CC, OR=32.99, 95%CI (11.40,95.42); and for CC+CT vs. TT, OR=0.04, 95%CI (0.02, 0.10). Sensitivity analysis performed according to different detection methods showed that for TT vs. CC, OR=6.03, 95%CI (1.53, 23.72); and for CC+CT vs.TT, OR=0.17, 95%CI (0.04, 0.68). ConclusionPolymorphism of MTHFR C677T gene may be associated with sensitivity to fluorouracil-based chemotherapy in patients with AGC.