The utilization of poly(epsilon-caprolactone) (PCL)/poly(methyl methacrylate-co-methacrylic acid)-based semi-Interpenetrating Polymer Networks as nanostructured precursors provides a straightforward and effective route for engineering COOH-functionalized nanoporous networks. Such functional frameworks can be used as cation-exchange supports in Ion-Exchange Chromatography for the separation of proteins, provided the structures contain a significant initial content of carboxylic acid functions. This investigation illustrates the major role played by the presence of the interconnected pores generated by the oligoester template in the protein retention. The resolution turns out to be better than that obtained with a classically prepared porous support using an organic solvent as a porogen.