Periodontal disease and DNA methylation markers have separately been associated with lung cancer risk. Examining methylation levels at genomic regions previously linked to periodontal disease may provide insight on the link between periodontal disease and lung cancer. In a nested case-control study drawn from the CLUE II cohort, we measured DNA methylation levels in 208 lung cancer cases and 208 controls. We examined the association between 37 DNA methylated CpG sites at three genomic regions, Homeobox 4 (HOXA4), Zinc finger protein (ZFP57) and a lcRNA gene region located in Chr10 (ENSG00000231601), and lung cancer risk. Statistically significant associations with lung cancer risk were observed for all 14 CpG sites from HOXA4 (odds ratio [OR] ranging 1.41-1.62 for 1 SD increase in methylation level, especially within 15 years) and one CpG site on gene ENSG00000231601 (OR=1.34 for 1 SD increase in DNA methylation level). While CpG sites on gene ZFP57 were not associated with lung cancer risk overall, statistically significant inverse associations were noted for six CpGs when restricting follow-up to 15 years (OR=0.73-0.77 for 1 SD increase in methylation level). Key methylation changes associated with periodontal disease are also associated with lung cancer risk. For both HOXA4 and ZFP57, that these associations were stronger within 15 years of follow up suggests that they act late in the natural history of lung cancer. Identifying biological pathways that link periodontal disease and lung cancer could provide new opportunities for lung cancer detection and prevention.