Abstract: Objective 　To explore the t ranscriptional expression and the promoter hypermethylation of Rasassociation domain family 1A gene (RASSF1A) and p16 gene, and the major mechanisms for silencing of these two genes in non-small cell lung cancer (NSCLC) in Chinese. Methods 　RT-PCR and Methylationspecific PCR (MSP) was used to detect the transcriptional expression and aberrant methylation of RASSF1A and p16 gene in 96 human NSCLC tissues and matched 96 normal lung tissues far from cancer area. Results 　(1) The transcriptional expression of RASSF1A and p16 gene was normal in all normal lung tissues far from cancer area but low or loss in 53. 12 %(51/ 96) carcinoma tissues for RASSF1A and in 36. 46 %(35/ 96) carcinoma tissues for p16 gene. (2) Of the 96 NSCLC samples, methylation was detected in 48. 96 % for RASSF1A, 34. 38 % for p16. RASSF1A methylation was observed 39 of 51 (76. 5 %) in NSCLC samples with obvious down-regulation expression of RASSF1A, 8 of 45 (17. 8 %) in cases in which the transcriptional expression of RASSF1A had no obvious change. The difference of two groups had statistical significance ( P < 0. 05) . p16 gene promoter hypermethylation was found 20 of 35 (57. 1 %) in cases with low or loss expression of p16 gene mRNA, 13 of 61 (21. 3 %) in cases in which transcriptional expression of p16 gene was normal. The difference of two groups had statistical significance ( P < 0. 05) . But no methylation was detected in 96 cancer-free tissues. Conclusion 　Loss or abnormal down-regulation of RASSF1A and p16 gene mRNA is a frequent event in patients with NSCLS in Chinese ; The promoter hypermethylation of RASSF1A and p16 gene may be the major mechanisms for silencing of these two genes in NSCLC.