The catalytic performance of titanosilicates involving hydrogen peroxide (H₂O₂) as the oxidant is strongly influenced by the solvents. Until now, there is still a lack of a universal principle that can guide the choice of a solvent. Herein, the kinetics of H₂O₂ activation catalyzed by various titanosilicates in different solvents is investigated, and an isokinetic compensation effect is concluded. This indicates that the solvent participates in the H₂O₂ activation process for the formation of a Ti–OOH species. Additionally, the results of isotopically labeled infrared spectra preliminarily confirm that the solvent acts as the mediator to promote the proton transfer during the H₂O₂ activation process. The catalytic activities of a series of TS-1 catalysts toward 1-hexene epoxidation are compared, which include Ti(OSi)₃OH species with a range of densities but a constant total Ti content. This reveals that the solvent effect is closely related to the Ti active sites of these TS-1 catalysts. Based on these results, a principle for the rational choice of solvent for this catalytic process is proposed. ROH is found to be the mediator for Ti(OSi)₄ sites, and methanol, which has a strong proton-donating ability, is the best solvent for these sites. However, for the Ti(OSi)₃OH sites, water (H₂O) is the mediator, and a weaker hydrogen bonding between H₂O molecules promotes proton transfer more effectively. The solvent influences the catalytic performance by perturbing the hydrogen bonds between the H₂O molecules, and aprotic acetonitrile, which has a strong ability to break the hydrogen bonding network between H₂O molecules, is the best solvent for Ti(OSi)₃OH sites. This study provides experimental evidence that the solvent promotes the catalytic performance of titanosilicates by assisting the proton transfer during the catalytic H₂O₂ activation process, which will pave the way toward the rational choice of solvent for the titanosilicate-catalyzed oxidation systems.