The current study was performed to assess any association between the methylenetetrahydrofolate reductase(MTHFR) C677T polymorphism and risk of lung cancer in Henan province. This case-control study involved94patients with newly histological confirmed lung cancer and 78 healthy controls. Genotyping was achieved withperipheral blood lymphocytes DNA and association of the polymorphism with risk of lung cancer was estimatedby unconditional logistic regression analysis. The frequencies of the MTHFR 667TT genotype were 37.2% in casescompared with 23.1% in controls (χ2 = 4.008, P = 0.045). Individuals with the 667CC/CT genotype displayed asignificantly reduced risk of lung cancer compared with those with the TT genotypes [adjusted odds ratio (OR),0.506; 95% confidence interval (95% CI), 0.258 – 0.991]. The C667T polymorphism might have a significanteffect on the occurrence of lung cancer in Henan province.