〔Abstract〕 Objective To explore the relationship between the methylation level of RABL6 in peripheral blood and early lung cancer(LC) with a case-control study in the Chinese population.Methods The methylation levels of 7 CpG sites in RABL6 gene in peripheral blood of samples from 275 LC patients(81.5% at stage I),and age-and gender-matched 185 benign lung nodule cases and 267 matched healthy controls were measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Multinomial Logistic regression adjusted for covariates was used to analyze the association between the RABL6 methylation and LC. Mann-Whitney U test was applied for the comparisons of RABL6 methylation levels between clinical characteristics subgroups of LC. Results Compared to the healthy controls,the methylation of RABL6 ＿Cp G ＿17 was inversely associated with LC in females( per-10% methylation: OR = 2. 47,95% CI = 1. 19-5. 13,P = 0. 016),but positively associated with LC in males( per-10% methylation: OR = 0. 52,95% CI = 0. 29-0. 94,P = 0. 030). In addition,hypermethylation of RABL6＿Cp G＿2 and RABL6＿Cp G＿5 was significantly associated with LC in the subjects older than 55 years( for RABL6＿Cp G＿2: per-10% methylation: OR = 0. 77,95% CI = 0. 60-0. 99,P = 0. 038; for RABL6＿Cp G＿5: OR = 0. 58,95% CI= 0. 34-0. 97,P = 0. 038). Conclusion The study reveals an association between peripheral blood-based RABL6methylation levels and early LC,providing a new clue for developing peripheral blood-based DNA methylation as a potential marker for the evaluation of LC risk.