Mesoporous silica aerogels have a wide range of potential applications in biotechnology, the food industry, pharmacy and medicine. Understanding the nature of the interactions of biomolecules with these porous nanostructured materials is essential for achieving optimum performance in the targeted applications. In this study, the well-characterized bovine serum albumin (BSA) was chosen as a model protein to probe protein–aerogel interactions in the solution phase. Aqueous BSA was mixed with suspended silica aerogel microparticles, and the colloid system was monitored on-line by UV–vis spectrophotometry and turbidimetry. The global mathematical analysis of the time-resolved data reveals that the fast sorption of the protein on the aerogel microparticles follows a multistep binding mechanism. The extensive sorption of the protein eventually induces the aggregation of the covered aerogel due to the alteration of the electrical double layer of the particles. The interaction of BSA and silica aerogel is the strongest between pH = 4 and 5, because their native surface charges are the opposite in this pH range, as indicated by their respective zeta potentials.