Rationally regulating the structure of catalysts in Fenton-like reactions provides abundant opportunities for the efficient remediation of organic micropollutants from the aqueous environment, yet it is challenging to achieve superior reactivity and the catalytic mechanisms have rarely been systematically elucidated. Herein, we present a simple strategy to synthesize confined catalysts with different pore-size distributions by modulating the proportion of β-cyclodextrin (β-CD) with a cavity. The degradation performance of the confined catalyst MCF with the smallest pore size (5.9 nm) was remarkably enhanced compared to the unconfined catalyst NCF, mainly by 1O2 and electron transfer. As the cavity content increases, the reactivity displayed an unexpected volcanic peak tendency. The pseudo-first-order reaction constant of MCF was 2.6 times higher than that of HCF (8.2 nm) in Fenton-like oxidation with peroxymonosulfate (PMS). Comparative control experiments demonstrated that the appropriate structure can significantly facilitate the diffusion and degradation process of pollutants that are adsorbed in the confined channels. The MCF/PMS system exhibited strong adaptability to coexisting ions and pH in the water matrix, and the intermediate products were harmless to the environment. This unusual catalytic mechanism and the structural regulation strategy will establish new insights into boosting the catalytic performance for the efficient removal of organic micropollutants.