This article reports on a case of stage IVB (cT2bN1M1c1) non-small cell lung cancer (NSCLC) with brain metastases harboring compound mutations in epidermal growth factor receptor (EGFR) exon 21 Leu858Arg and mitogen-activated protein kinase 1 (MEK1) exon 3 lle112Thr and with a high program death ligand 1 (PD-L1) expression that successfully underwent radical lung cancer surgery following combined therapy. The gene discussed is MAPK1; the disease is lung cancer.