Objective：To examine the relationship between N5，10-methylenetetrahydrofolate reductase（MTHFR） C677T gene poly－morphism and nonneoplastic epithelial disorders of vulva（NNEDV），and its possible mechanism of action. Methods：The clinical data of 60 patients NNEDV confirmed by biopsy（study group） and 46 healthy women（control group） in our hospital between August 2016 to June 2018 were reviewed. MTHFRC677T gene polymorphism was compared between the two groups. In addition，MTHFRC677T gene polymorphism and serum folic acid and serum homocysteine levels were also compared between patients with different histopathologic types of NNEDV. The study group included 21 cases of vulvar lichen simplex chronicus（LSC） and 39 cases of vulvar lichen sclerosus（LS）. Results：The frequencies of the MTHFR 677TT genotype and T allele were significantly increased in the study group（13.3% and 38.3%，respectively） than in the control group（4.3% and 21.7%，respectively）（ χ2=6.851，P=0.033； χ2=6.688，P= 0.010，respectively）. Compared with the control group，LSC patients had significantly increased frequencies of MTHFR 677TT genotype（23.8%） and T allele（45.2%）（ χ2=7.572，P=0.023； χ2=7.717，P=0.005，respectively）. In contrast，there no significant differences in the frequencies of the MTHFR 677TT genotype（7.7%） and T allele（34.6%） between LS patients and controls（both P>0.05）. Com－pared with the CC genotype，the CT（OR=2.386，95%CI=1.046 to 5.443） and TT（OR=5.091，95%CI=0.981 to 26.430） genotypes might increase the risk of NNEDV. In patients with the MTH－FR677CC，CT，and TT genotypes，serum folic acid level signifi－cantly decreased（F=4.386，P=0.018） and serum homocys－teine level significantly increased（F=4.978，P=0.012） as the number of T mutations increased. However，there were no sig－nificant differences in serum folic acid and homocysteine levels between LSC and LS patients（both P>0.05）. Conclusion：Serum folic acid and homocysteine dysmetabolism induced by MTHFRC677T gene mutation may be associated with the development of LSC.