The mechanism analysis reveals that GM‐protac can influence the BIM‐associated apoptosis pathway, c‐Met, PD‐L1, HER‐2, NF‐κB or PI3K‐AKT signaling pathway, etc. Meanwhile, they displayed obvious tumor inhibition with negligible toxicity in both osimertinib and gefitinib‐resistant lung cancer animal models. The gene discussed is NFKB1; the disease is lung cancer.