Abstract: Objective To investigate the effect of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation,the interaction between MTHFR C677T mutation and environmental factors on esophageal cancer(EC).Methods The case-control design was used and newly diagnosed EC patients were recruited as subjects Polymerase chain reaction-restricted fragment lengthpolymoiphism (PCR-FLP) was perform ed to detect MTHFR gene C677T mutation The intemction between MTHFR gene C677T mutation and environmental risk factors was evaluated by multiple logistic regression analysis.Results There was a synergism between MTHFR gene C677T mutation and alcohol drinking index,taking hot food and drinks,taking moldy food,mental status,and the age with the odds ratios of 10.892(P=0.013 8)，12.043(P=0.012 4)，16.444 (P=0.009 6)，20.581 (P≤0.000 1) and 5.201 (P=0.014 5)，respectively.Conclusion MTHFR gene C677T mutation can increase risks of EC in elders and subjects with alcohol drinking,taking hot food and drinks,taking moldy food,and bad mental status.