Abstract: Objective To detect the methylation status of the death associated protein kinase (DAPK) gene in the plasma of non-small cell lung cancer (NSCLC) patients, and to evaluate its clinical significance in screening and early diagnosis of NSCLC. Methods 112 cases of NSCLC patients and corresponding control cases were enrolled, by using nested methylation-specific polymerase chain reaction (nMSP), we determined the methylation status of the DAPK gene in the lung cancer tissues，adjacent tissues，plasma from peripheral blood and 112 normal control blood samples. The result of each group was compared. Results The total frequency of the DAPK gene methylation was 59.8% in NSCLC tissues, significantly higher than that in the adjacent tissues at 8.0% (P＜0.001). Compared to adjacent tissues groups, the hypermethylation frequency in the lung cancer tissues exhibited significant difference in squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma (P＜0.001).The hypermethylation frequency for DAPK gene was 21.4% in the plasma of the 112 NSCLC cases, without positive result in the plasma of the control group (P<0.001). The hypermethylation frequency in plasma did not significantly correlate to the clinical classification, pathologic type and clinical staging of the NSCLC. Conclusion Detection of the DAPK gene methylation in the plasma of NSCLC patients may provide valuable information for early screening and diagnosis of the NSCLC.