In this work, the encapsulating peroxo-polyoxometalate in the mesoporous of metal-organic framework (MIL-101(Fe)) to synthesize composite according to the principle of host-guest matching. The structure of the host-guest composite was analyzed by a variety of methods, and the catalytic activity for desulfurization was investigated under mild conditions. The composites combine the advantages of peroxo-polyoxometalate (high efficiency) and MIL-101(Fe) (good recyclability and high porosity), showing synergistic effect between host and guest. The sulfur-containing organic compounds in simulated liquid fuel can be almost completely removed under the catalysis of PW4@MIL-101(Fe). The catalyst PW4@MIL-101(Fe) can be reused for 10 times without prominent decrease in desulfurization activity, indicating that it has good reusability due to the confinement effect between the window size of MIL-101(Fe) and molecular size of PW4. In addition, several control experiments and electron spin resonance experiment were researched to explore the possible mechanism, and the results show that the active component in the catalyst can promote the decomposition of H2O2 into ·OH and thus accelerate the desulfurization reaction. This work discloses a facile and environmentally friendly method to prepare the "host-guest matching" catalyst with high activity and stable reusability, which provides ways for further developments in heterogeneous catalyst based on POM and MOF.