In this work, the surface-protein interfacial noncovalent interactions are generated and tuned as hydrogen bonding, hydrophobic affinity, electrostatic interaction, and additional pi-pi overlapping through designing suitable surface property with different chemical moieties and varying the pH of adsorption medium. The heterogeneity of lysozyme (Lz) adsorption is investigated. It has been found that the interfacial interactions of support surfaces and the protein play a key role in the adsorption kinetics, adsorption capacity, distribution states, and adsorption reversibility of Lz, while the protein-protein repulsion makes impact dependently on the nature of surface-protein interactions. The pi-pi overlapping is another significantly crucial driving force in addition to the electrostatic force, hydrophobic interaction, and hydrogen bonding that commonly drive protein adsorption. But the hydrogen bonding between surface NH2 and Lz is exceptionally not sufficient to drive Lz adsorption. The adsorption of Lz on functionalized mesoporous silica is partial reversible and makes no damage oil the protein secondary structure. (C) 2008 American Institute of Chemical Engineers.