Objective To analysed association of methylation changes of CpG islands for multiple tumor suppressor genes promoter domain with non-small cell lung cancer.Methods Methylation Specific PCR was used to detect methylation of tumor suppressor genes(TSG)and the data were analysed by non-codition logistic regress analysis.Results The data of 94 cases with lung cancer were analysed.The results declared that 91.49 percent of lung cancer tissue were discovered methylations for more than one TSG in comparison with normal lung tissue(p<0.01).Frequencies of P 16INK4a,DAPK,MGMT,TIMP-3 and RARβ were 41.49%,50.00%,17.02%,24.47% and 68.09%,respectively,compared with that of normal lung tissue.Effects of TSG methylation on squamous cell cancer,center cancer,stage Ⅲ or more were greater and was increased with methylation index(MI).Smoking increased the risk of p16rNIK4a and DAPK methylation by OR of 21.714 and 15.268(p<0.01),respectively.There is dose-response relationship between smoking duration,smoking index and methylation of TSG.Conclusion smoking is the important risk factor of methylation for TSG and the methylation of multiple TSG play a key role in the pathogenesis of lung cancer.