In summary, SHP2 is an intracellular target of embelin that can reduce the malignant phenotype of KRAS‐mutant NSCLC in vivo and ex vivo by co‐targeting XIAP and SHP2 to inhibit multiple cancer‐related pathways to reverse EMT, overcome the negative feedback of the MAPK signaling pathway, and induce apoptosis in tumor cells, thus providing a novel approach to address the apoptosis tolerance and adaptive resistance of KRAS‐mutant tumors. Here, KRAS is linked to non-small cell lung carcinoma.