When the MTHFR 677CC genotype was used as the reference group, the MTHFR 677 CT genotype were associated with a significantly reduced risk in squamous cell carcinoma (OR = 0.78; 95% CI = 0.64- 0.96), the combined variant genotypes (677 CT + TT) also showed a protect effect on the risk of squamous cell carcinoma (OR = 0.79; 95% CI = 0.65- 0.95), while there was no significant association in other histological types of lung cancer. Here, MTHFR is linked to squamous cell carcinoma.