The current study showed that in T790M‐mutated EGFR‐TKI‐resistant cell line H1975, downregulation of MAP4K4 inhibited ERK activation in the presence and absence of erlotinib treatment (Fig. 3G), implying that MAP4K4 bypasses EGFR to promote ERK activation; that is, MAP4K4 functioned in parallel with EGFR to regulate ERK activation, which in turn suggests that suppressing ERK reactivation through targeting MAP4K4 in lung adenocarcinoma could be a novel strategy to overcome EGFR‐TKI resistance. This evidence concerns the gene MAP4K4 and lung adenocarcinoma.