A mesostructured ionic liquid–polyoxometalate (IL-POM) hybrid has been prepared through designing a new dihydroxy-tethered guanidinium-based IL, N′′-(2,3-dihydroxypropyl)-N,N,N′,N′-tetramethylguanidinium chloride, to interact with Keggin-type POM phosphotungstic acid (H3PW) in a self-assembly process. Scanning electron microscopy and transmission electron microscopy showed its special coral-shaped micromorphology. Nitrogen sorption analysis indicated the formation of a porous structure with a moderate surface area of about 30 m2 g−1 and narrowly distributed pore size located in the mesoscale. Assessed in the cis-cyclooctene epoxidation with H2O2, the mesostructured hybrid exhibited superior heterogeneous catalytic activity and steady reusability, and the conversion was more than four times that of homogeneous H3PW itself, and more than 14 times that of the nonporous analogues. On the basis of the experimental results, a unique “substrate–solvent–catalyst” synergistic mechanism is proposed and discussed for understanding the dramatically enhanced catalytic performance.