In this study, we found that the KEAP1 mutation is a strong indicator of ferroptosis resistance in NSCLC and is accompanied by the activation of various NRF2 target genes, such as FSP1, NQO1, SLC7A11, GPX2, SRXN1, and GCLC, by investigating omics datasets obtained from over 1,000 cancer cell lines and hundreds of primary cancer tissues. This evidence concerns the gene GCLC and cancer.