This dataset was generated using a crosslinking immunoprecipitation–mass spectrometry (IP–MS) approach to identify proteins interacting with Actin. Cultured cells were mildly fixed with formaldehyde to preserve protein–protein interactions, quenched, and lysed under gentle detergent conditions. Actin-associated complexes were immunoprecipitated using antibody-coupled magnetic beads, while IgG beads served as negative controls. The recovered proteins were then subjected to proteomic analysis to define the Actin interactome and distinguish specific interaction partners from background binders.