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. Here, PIK3CA is linked to non-small cell lung carcinoma.