BACKGROUND Variations in the methylene tetrahydrofolate reductase (MTHFR) gene have been reported as risk factors for numerous conditions, including cardiovascular disease, thrombophilia, stroke, hypertension and pregnancy-related complications. Moreover, it was reported there is an association between breast cancer and mutations inMTHFR-C677T. However, whether there is an association betweenMTHFRgene polymorphism and granulomatous lobular mastitis or not has been rarely investigated. AIM To analyze the association betweenMTHFRgene polymorphism and granulomatous lobular mastitis. METHODS Fifty-one patients with granulomatous lobular mastitis admitted to The First Hospital of Kunming were selected as study samples. Their hospitalization time ranged from February 2018 to February 2019. The 51 patients were included in the experimental group, and another 51 women who underwent physical examination at The First Hospital of Kunming in the same period were included in the control group. Deoxyribonucleic acid andMTFR genetic polymorphism testing were performed in each group. The association betweenMTHFRgene polymorphism and granulomatous lobular mastitis was observed. RESULTS There were significant differences in genotype frequency and allele frequency of C/C and C/T between the experimental group and the control group (allP< 0.05). However, there was no significant difference in frequency of T/T genotype between the two groups (P> 0.05). In addition, there was no significant difference in genotype frequency and allele frequency of A/A, A/C and C/C between the two groups (P> 0.05). CONCLUSION MTHFRgene C677T locus polymorphism is closely related to granulomatous lobular mastitis.