In this study, we aim to investigate the therapeutic potential of PLK1 inhibition in EGFR-mutant NSCLC, aiming to elucidate the mechanisms underlying the synergistic antitumor effects achieved through co-targeting the EGFR/ERK and PLK1/STAT3 signaling pathways, as well as the capacity of these synergistic effects to overcome acquired resistance to EGFR-TKIs. This evidence concerns the gene STAT3 and non-small cell lung carcinoma.