Embelin cotargets SHP2 to disrupt the SHP2/GRB2/SOS complex, inhibiting cancer‐related signaling pathways such as MAPK, (PI3K)/AKT pathway, and XIAP to induce apoptosis signaling pathway, respectively, leading to synthetic lethality in KRAS‐mutant NSCLC cells both in vivo and in vitro. This evidence concerns the gene AKT1 and non-small cell lung carcinoma.