Abstract: Objective To explore the relationship between polymorphisms of estrogen synthesis and metabolism related genes and susceptibility of non-smoking female lung cancer and to provide new genetic susceptibility markers for female lung cancer research.Methods A hospital based case-control study was conducted.Totally 516 unrelated Han non-smoking females with lung cancer and 516 unrelated Han non-smoking females with diseases other than respiratory system disease and tumor were selected as a case group and a control group, respectively, from a level 3 first-class hospital in Shenyang, Liaoning province from January 2004 to December 2012.Questionnaire survey and genotyping were conducted to study the relationship.Results The risk of lung cancer increased by 60%for individuals carrying G/A genotype than those carrying wild homozygous G/G genotype of rs4680 after adjusting for age and cooking smoke exposure(odds ratio(OR)=1.60, 95% confidence interval(95%CI)1.23-2.08);the risk of lung cancer increased by 57%for individuals carrying G/A or A/A genotype than those carrying wild homozygous G/G genotype(OR=1.57, 95%CI:1.22-2.01).No significant correlation was found between rs743572, rs10046 and rs605059 polymorphism and risk of lung cancer.Conclusion Polymorphism of rs4680 of catechol-O-methytransferase may be a potential genetic susceptibility loci of lung cancer for Han non-smoking women in China.