We found that the MTHFR C677T polymorphism was substantially associated with luminal B and TNBC susceptibility and exerted a protective effect against the risk of luminal A. Moreover, this study indicated that TNBC patients with the MTHFR C677T polymorphism are associated with hypertension, and the same gene polymorphism in luminal B breast cancer patients may be associated with certain clinical characteristics, such as diabetes mellitus and increased BMI. Here, MTHFR is linked to breast cancer.