A one-step sol-gel synthesis method was employed to fabricate cobalt-doped silica aerogel (Co@Si-A) catalysts in this study, which were subsequently applied for activating peroxymonosulfate (PMS) to degrade tetracycline (TC). The experimental results demonstrated that the catalyst with a 25wt% cobalt doping ratio (25Co@Si-A) exhibited the most superior catalytic performance, achieving an exceptionally high TC degradation efficiency of 98.97% under the specified test conditions. Brunauer-Emmett-Teller (BET) analysis revealed that the 25Co@Si-A catalyst possessed a high specific surface area and a well-developed porous architecture rich in nano-confined spaces. The synergistic 25Co@Si-A/PMS system displayed outstanding adaptability, effectively operating over a broad pH range from 5 to 9. Furthermore, the system demonstrated strong resistance to interference from sulfate (SO_4^(2-)) and nitrate (NO_3^-) ions. To elucidate the underlying reaction mechanisms, comprehensive analyses were conducted, including electron paramagnetic resonance (EPR) spectroscopy, radical quenching experiments, and probe compound tests. These investigations collectively confirmed that the highly efficient degradation of TC through the 25Co@Si-A/PMS system was attributed to a synergistic combination of radical and non-radical pathways. The primary reactive species involved were free radicals, dominated by sulfate radicals (SO_4^(2-)) with contributions from hydroxyl radicals (?OH), and non-radical singlet oxygen (1O2). The degradation mechanism was further enhanced by the nano-confined effect inherent to the aerogel's structure. This effect promoted several key processes: the concentration and enrichment of reactant molecules (both PMS and TC) within the pores, the increased exposure and accessibility of active catalytic sites, and the enhancement of electron transfer efficiency, which is crucial for the reaction. In conclusion, this research provides a novel and promising strategy for utilizing silica aerogel-based materials to activate PMS for the effective removal of tetracycline. The study offers substantial theoretical insights and crucial technical support for the future development and design of innovative cobalt-based catalytic materials supported on silica aerogels for advanced oxidation processes in water treatment applications.