In this study we have investigated how different proteins interact with big organic ions. Two ions that are similar in size and chemical structure (Ph4B- anion and Ph4As+ cation) were studied. The proteins chosen are the two major allergenic proteins of cow's milk, β-lactoglobulin and β-casein, and bovine serum albumin, BSA, as the reference protein. First, a quantitative study to determine the hydrophobic degree of the proteins was performed. Then, electrokinetic and stability measurements on protein-coated polystyrene (PS) microspheres as a function of the tetraphenyl ion concentration were carried out. Our results show that the affinity of the organic ions depends on the hydrophobicity of the interface. Big charge inversions and re-stabilization patterns were observed at very low concentrations of tetraphenyl ions for the most hydrophobic protein studied (with β-casein). Besides, the ionic concentrations needed to destabilize these colloidal systems were roughly one order of magnitude lower for the anion than for the cation. In addition, we studied conformational changes of the adsorbed proteins with a quartz crystal microbalance. Proteins were adsorbed onto hydrophobic flat substrates and then exposed to the tetraphenyl ions. The protein films swelled or collapsed as a function of the accumulation of tetraphenyl ions. Similarly to the electrokinetic/stability studies, the ionic concentration necessary to trigger structural changes of the protein films was one order of magnitude larger for the cation than for the anion. All the results evidence that the accumulation of these organic ions on an interface depends directly on its degree of hydrophobicity. We attribute the different interactions of the anion and the cation with these interfaces to their dissimilar hydration, which makes the anion show a more hydrophobic behaviour than the cation.