In this study, using patient‐derived lung adenocarcinoma (LUAD) organoids and genetically modulated cancer cell lines, we provide data to uncover an unrecognized hypoxia/calcium/calmodulin‐dependent protein kinase 2 isoform A (CaMK2A)/nuclear factor erythroid 2‐related factor 2 (NRF2)/GSTP1 axis in lung cancer and demonstrate its role in CSC regulation. The gene discussed is CAMK2A; the disease is lung cancer.