We found an effect of EGFR-TKIs resistance on DNA methylation in favor of lung carcinogenesis via multiple tumor progression pathways, among which the specific downregulation of MUC17 by UHRF1/DNMT1-mediated promoter methylation promote the activity of NF-κB by inhibiting the expression of MZF1, has implications in evaluating drug resistance. Here, EGFR is linked to neoplasm.