Enzymes have unique structures, with various amino acid residues encapsulating metal active sites. Their high performance is mainly achieved via weak interactions between the functional groups and the substrate. Inspired by the enzyme structure, we designed an encapsulated catalyst (E-S=O) wherein AuPd nanoparticles were encapsulated by porous organic frameworks (POFs) modified with S=O groups. The alcohol reaction rate of E-S=O increased 2-fold compared with the control catalyst without S=O groups. The hydrogen bond was formed between alcohol and S=O groups, which was confirmed via 1H NMR and inverse-phase gas chromatography (IGC) tests. Further insight including adsorption isotherm, in situ diffuse reflective infrared Fourier transform spectroscopy (DRIFTS), and the kinetics data confirmed the hydrogen bond could account for the rate enhancement. The proposed catalyst preparation strategy through precise microenvironment control via hydrogen bonds with substrates paves a new way for high-performance catalyst design.