Ion-exchange chromatography offers cost-effective, rapid, and efficient separations and is widely used for the concentration and purification of proteins. The use of classical ion-exchange resins, however, is not always optimal, particularly under high salt conditions. We describe the use of surface plasmon resonance (SPR) spectroscopy and self-assembled monolayers (SAMs) to understand the characteristics of surfaces that promote the adsorption of proteins at high ionic strengths (high-salt conditions). We synthesized SAMs presenting different multi-modal ligands, and determined the influence of surface composition, solution composition, and the nature of the protein on the extent of protein adsorption onto the SAMs. Our results confirm that hydrophobic interactions can contribute significantly to protein adsorption under high-salt conditions. The combination of SPR and SAMs is well-suited for elucidating the fundamental physics underlying the interaction of proteins with complex surfaces of relevance to chromatography.