We assessed the association between dietary intake of folate and the MTHFR genotype with breast cancer in a Chinese population, with additional analysis of the interactions of gene polymorphisms and dietary intake of folate, vitamin B-6, and vitamin B-12. A case-control study was performed, and 535 patients with newly diagnosed breast cancer and 673 controls were enrolled into this study. The MTHFR 667TT genotype (odds ratio (OR)= 1.82, 95 % confidence interval (CI)= 1.24-2.97) and T allele (OR 0= 1.48, 95 % CI= 1.15-1.78) were correlated with a moderately significant increased risk of breast cancer when compared with the CC genotype. Individuals carrying the MTR 2756GG genotype (OR= 1.66, 95 % CI= 1.16-2.56) and G allele (OR= 1.42, 95 % CI= 1.26-1.81) had a higher risk of breast cancer when compared with subjects with the AA genotype. The MTHFR 667 T allele and MTR 2756 G allele were associated with a higher risk of breast cancer in individuals with low folate intake, vitamin B-6, and vitamin B-12, but the association disappeared among subjects with moderate and high intake of folate, vitamin B-6, and vitamin B-12. This case-control study found that the MTHFR C677T and MTR A2756G polymorphisms are associated with risk of breast cancer, and folate, vitamin B-6, and vitamin B-12 intakes influence these associations.