Objective To assess the relationship between single nucleotide polymorphism(SNP) of thioredoxin gene TXN and the susceptibility of lung cancer in Chinese Han population. Methods A casecontrol study on 292 cases with histologically confirmed lung cancer and 307 age and gendermatched cancerfree controls of Chinese Han population was performed. The selected 9 SNP sites were genotyped by PCR with iPLEX technique. Results Significant differences of the frequency were observed in 3 SNP of TXN gene: rs2776, rs4135220 and rs4135212 between lung cancer paitients and controls. The subjects who carried mutated alleles on rs2776rs4135220 showed a 0.77 times increase of lung cancer risk (95%CI=1.102.84), while a 1.24 times increase of risk for those who carried mutation on rs4135212 (95%CI=1.293.89) in a dominant model. An increased risk for lung cancer was observed in stratification analysis for smoking quantity. Lowgrade smokers carrying rs2776rs4135220 mutation showed a 0.75 times increase of lung cancer risk (95%CI=1.01-3.04) and a 1.46 times increase (95%CI=1.29-3.04) for those who carried rs4135212 mutation. Conclusions The results of this study support that the SNP of rs2776, rs4135220 and rs4135212 in TXN gene may associate with lung cancer susceptibility in Chinese Han population. The lung cancer risk may rise in nonsmokers and lowgrade smokers carrying mutations on the 3 SNP sites.