In this study, we (1) systematically analyzed endogenous EGFR phosphorylation changes to identify distinct EGF dependency in different EGFR genotypes in lung cancer cells; (2) demonstrated a novel relationship between AURKA and EGFR, which might be mediated via an AURKA-elicited phosphorylation event at EGFR-Thr654 and -Ser1046 in lung cancer cells; and (3) determined the expression of AURKA, EGFR-Thr654 and EGFR-Ser1046 in lung adenocarcinoma tissues. Here, EGFR is linked to lung adenocarcinoma.