As the remarkable prevalence of activated protein tyrosine kinases (TKs) as oncoproteins and their mutations being identified in numerous cancers, the control of protein tyrosine phosphorylation has been considered to play a central role in ensuring the homeostasis of cellular physiology and thus, preventing tumorigenesis. Protein tyrosine phosphatases (PTPs) can contribute to this equilibrium of protein tyrosine phosphorylation and thereby antagonize the oncogenic activities of tyrosine kinases, therefore, PTPs are prominently considered to act as tumor suppressors. To achieve a comprehensive understanding of the protein-protein interaction network for this PTP family, we isolated the ~ 70 PTP-associated protein complexes from HEK293T cells and provided a systematically proteomic analysis for this tumor suppressor family.