Significant associations were identified between polymorphic variation in MTHFS, MTHFR and MTRR. Under the Cox proportional hazards model, the HRs for OS from all lung cancer associated with MTHFS Thr202Ala heterozygosity, homozygosity and carrier status were: 1.53 (95% CI: 1.17–2.01), 1.04 (95% CI: 0.38–2.84) and 1.49 (95% CI: 1.14–1.94), respectively. Here, MTHFR is linked to lung carcinoma.