Our results showed that induction of PD-L1 by EGF stimulation was only detected in EGFR-mutated NSCLC cell lines, such as H1975 and PC-9...Our findings suggested that MUC3A deficiency improved EGFR-mutated NSCLC sensitivity to tyrosine kinase inhibitors via increasing EGFR protein stability and decreasing PD-L1 expression through PI3K/Akt and MAPK pathways. Mice inoculated with MUC3A deficiency tumor cells treated with AZD-9291 had the fastest tumor regression and delayed relapse.