Epidermal growth factor receptor (EGFR) is an important receptor tyrosine kinase protein. Activated EGFR promotes downstream signal transductions through phosphorylation, and its phosphorylation has been implicated in pathologies including many types of cancers. Previously, our lab has developed the phosphorylation targeting chimera (PhosTAC) to achieve targeted dephosphorylation of proteins of interest. In this study, harnessing a tyrosine phosphatase (PTPN2) for the first time, we designed and synthesized a series of PhosTACs to dephosphorylate wild-type and mutant EGFR. We demonstrated efficient EGFR dephosphorylation with the treatment of PhosTACs. Phosphoproteomics was used to confirm PhosTAC induced dephosphorylation as well as its different inhibitory patterns from the warhead gefitinib. Consistent with EGFR dephosphorylation, EGFR PhosTACs induced apoptosis and inhibited cell proliferation. As RTKs are critical receptors for cellular signaling and targeted therapies, these tyrosine-phosphatase recruiting PhosTACs showcased their potential of modulating RTKs, expanding the scope of bifunctional molecules utility.