AbstractIt was previously demonstrated that the WNT/β‐catenin pathway is present and active in platelets and established that the canonical WNT ligand, WNT‐3a, suppresses platelet adhesion and activation. In nucleated cells, β‐catenin, the key downstream effector of this pathway, is a dual function protein, regulating the coordination of gene transcription and cell–cell adhesion. The specific role of β‐catenin in the anucleate platelet however remains elusive. Here, a label‐free quantitative proteomic analysis of β‐catenin immunoprecipitates from human platelets is performed and nine co‐immunoprecipitating proteins are identified. Three of the co‐immunoprecipitating proteins (α‐catenin‐1, cadherin‐6, and β‐catenin‐interacting protein 1) are common to both resting and activated conditions. Bioinformatics analysis of proteomics data reveal a strong association of the dataset with both cadherin adherens junctions and regulators of WNT signaling. It is then verified that platelet β‐catenin and cadherin‐6 interact and that this interaction is regulated by the activation state of the platelet. Taken together, this proteomics study suggests a novel role for β‐catenin in human platelets where it interacts with platelet cadherins and associated junctional proteins.