Abstract: Objective To explore correlations between 5,10 methy lenetetrahydro folate reductase(MTHFR)s C677T genetic pointmutation,exposure to chemicals during pregnancy and congenital heart disease(CHD).Methods A total of 144 cases and 168 controls were selected for the case control study and MTHFRC677T genotype was determined by poly merase chain reaction restricted fragment length polymorphism(PCRRFLP).Indicators of quantitative analysis for the in tensity of interaction between MTHFR gene C677TT and exposure to chemicals were analyzed with stratified Logistic multiplicative regression.Results The risks of CHD for subjects with geno type MTHFR 677TT was 3.215 times(95% CI:2.042 -5.784)higher than the subjects with genotype MTHFR 677CT or CC.The OR of CHD for exposure to chemicals during pregnancy was 2.150(95% CI:1.958-5.280).There was additive interaction effect between genotype MTHFR 677TT and exposure to chemicals during pregnancy.The relative excess risk due to interaction(RERI),the a ttributable proportion due to interactionAP(AB)and the proportion of in teraction effect between purefactorsAP*(AB)were 4.938,60.23%,68.59%,respectively.Conclusion The in teraction of MTHFRC677T genetic point mutation and exposure to chemicals during pregnancy may increase the risks of CHD of off spring in pregnant women.