Abstract: Objective To investigate the value of methylenetetrahydrofolate reductase A1298 C(MTHFR A1298 C) gene polymorphism in the treatment of hyperhomocysteinemia(Hcy). Methods According to the results of MTHFR A1298 C gene detection, 236 patients of Han people with ischemic stroke complicated with HHcy in Xuchang Central Hospital from February 2017 to September were divided into three groups: A(type AA gene), B(type AC gene) and C(type CC gene). There were 146 cases(61.86%), 68 cases(28.81%) and 22 cases(9.32%) in the group A, B and C respectively. The three groups were treated with folic acid tablets to reduce Hcy treatment on the basis of the routine treatment of ischemic stroke. The changes in plasma Hcy were recorded before and 3 months and 6 months after the treatment of folic acid. Results The plasma Hcy in 3 months and 6 months of the group A were(22.21±4.62) μmol/L and(13.63±4.15) μmol/L,which was significantly lower than that before taking medicine(27.92±5.24) μmol/L. The plasma Hcy in 6 months of the group B and C were(18.58±5.43) μmol/L and(21.05±6.12) μmol/L respectively, which was significantly lower than that before taking medicine(29.13±6.82) μmol/L and(31.82±4.48) μmol/L. After taking folic acid tablets for 6 months, the plasma Hcy decline rate in group A was(51.39±9.47)%, which was significantly higher than that in group B [(37.42±11.46)%] and C [(34.19±10.53)%]. Conclusion MTHFR A1298 C gene polymorphism significantly affects the therapeutic effect of folic acid on the reduction of plasma Hcy, and the detection of MTHFR A1298 C gene polymorphism is of certain guiding value in the treatment of hcy.