Overall, our results showedthat genotype distribution of MTHFR rs4846048 and rs4845882polymorphisms was not different between HCC patients and controls.MTHFR rs9651118 and rs1801133 loci were protective factorsfor HCC (rs9651118: CT vs. TT: adjusted odds ratio (OR) = 0.67,95% confidence interval (CI): 0.49–0.90,P=0.008 and TC/CC vs. TT: adjusted OR = 0.70,95% CI: 0.53–0.93, P=0.015; rs1801133: GAvs. Here, MTHFR is linked to hepatocellular carcinoma.