Abstract: Objective To explore the relationship between the methylenetetrahy drofolate reductase（MTHFR） A1298C polymorphism and susceptibility to hepatocellular carcinoma（HCC）. Methods A preformulated search strategy was used to search the English-and Chinese-language research literature on the association between the MTHFR A1298C polymorphism and HCC.The strength of the association was assessed in terms of odds ratios（ORs） and 95% confidence intervals（CIs），and heterogeneity was evaluated.All analyses were conducted using Stata 12.0. Results A total of six case-control studies involving 1 708 cases and 2 911 controls met the inclusion criteria.Significantly reduced risk of HCC was found in the homozygote comparison（CC vs AA：OR 0.55，95%CI 0.38~0.79，P=0.001） and recessive model（CC vs AC/AA：OR 0.54，95%CI 0.38~0.78，P=0.001）.However，no significant increase or decrease in risk was found in the additive model（C vs A：OR 0.95，95%CI 0.85~1.06，P>0.05）.No publication bias was found using any of the genetic models. Conclusions Genotype CC of MTHFR A1298C may decrease the risk of HCC and may therefore constitute a protective factor for HCC.

Key words: Liver neoplasms, Methylenetetrahy drofolate reductase, A1298C, Genetic polymorphism, Susceptibility, Meta-analysis