In this study, we emphasized the necessity and effectiveness of combined use in resistant cancer treatment and, for the first time, revealed that apigenin + gefitinib combination inhibits AMPK signaling pathway and oncogenic drivers c-Myc, HIF-1α, and EGFR and damages the glucose uptake and utilization on EGFR mutant-resistant NSCLC cells. The gene discussed is HIF1A; the disease is non-small cell lung carcinoma.