SBA-15 mesoporous materials were synthesized with different pore sizes (5 and 10 nm) and thiol-functionalized groups and then characterized to describe their ability to differentially adsorb β-lactoglobulin (BLG), a globular protein with an ellipsoid shape measuring 6.9 nm in length and 3.6 nm in width. All adsorption experiments showed that the adsorption capacities of mesoporous materials for BLG were dependent of the duration of contact between the two materials (mesoporous and BLG) and the initial BLG concentration. It was also shown that the pore sizes and thiol groups of SBA-15-based adsorbents are an important factor for the BLG adsorption capacities. Among the tested adsorbents, thiol-functionalized SBA-15 with 10 nm pore size (SBA-15-SH-10) showed the highest adsorption capacity (0.560 g.g-1) under optimal experimental conditions. Kinetics studies demonstrated that the adsorption occurs predominantly inside the pores with interactions occurring on heterogeneous surfaces. In addition, the thermodynamic parameters indicate a spontaneous and exothermic behavior of BLG adsorption process onto the thiol-functionalized SBA-15 mesoporous adsorbent. Finally, the characterization of SBA-15-SH-10 adsorbent at 308 K showed the occurrence of an oxidation reaction of the thiol groups to sulfonate groups during the adsorption process as confirmed by Raman spectroscopy. The spectra recorded after adsorption of the protein showed that this adsorption did not impact the secondary structure of the protein.