Due to the inevitable acquired resistance and kinase-independent functions of EGFR, targeting EGFR degradation by small molecules is a promising cancer treatment strategy.33 Here, we identified the 23-HBA derivative DPBA that induces EGFR degradation by directly binding to EGFR ECD, blocking downstream pathways and thereby suppressing NSCLC growth. Here, EGFR is linked to non-small cell lung carcinoma.