To help clarify whether the MTHFR variants are associated with susceptibility of ischemic stroke and total serum homocysteine (tHcy) level, we examined nine tag SNPs (single nucleotide polymorphism) in the MTHFR gene (rs12121543, rs13306561, rs13306553, rs9651118, rs1801133, rs2274976, rs4846048, rs1801131, rs17037396) in a case-control study in the Chinese population. This evidence concerns the gene MTHFR and ischemic stroke.