Two Cu/ZrO2 catalysts defect with different microenvironments and electronic structures (CZ-ag-70 and CZ-va catalysts) were synthesized by the same oxalic-acid-complexation-based method but different heat-treatment methods, and they were used to catalyze the hydrogen-transfer reaction between 5-hydroxymethylfurfural (HMF) and isopropanol. The structure–activity relationship of each catalyst was analyzed, and defect microenvironments were found to have an important influence on the product of the hydrogen-transfer reaction. The CZ-ag-70 catalyst was rich in Cuδ+- VZr+ interfacial sites (the interfacial sites between electron-deficient copper active sites (Cuδ+)) and electron-free zirconium vacancies (VZr+), and it was conducive to the formation of dehydroxylation product 2,5-dimethylfuran (DMF). Specifically, the ca-ag-70 catalyst achieved 100 % HMF conversion and 82.2 % DMF selectivity. On the other hand, the CZ-va catalyst was rich in single-electron zirconium vacancies (VZr∙), and it was conducive to the generation of reductive-etherification product 2,5-bis(propoxymethyl)furan (BPMF) (100 % HMF conversion and 55 % BPMF selectivity). Through X-ray diffraction spectrum (XRD), electron spin resonance (ESR), hydrogen temperature-programmed reduction (H2-TPR), in-situ Fourier-transform infrared spectroscopy (in-situ FTIR), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) analyses, the structure of the CZ-ag-70 catalyst and the mechanism of defect formation in the catalyst were analyzed. The precursor of the CZ-ag-70 catalyst first formed a copper-doped zirconium oxalate substrate. Then, under 500 ℃ reducing atmosphere, the substrate was converted into a copper-doped tetragonal-zirconia carrier, some of the copper species doped into the crystal lattice of the tetragonal-zirconia carrier were reduced, and the copper species migrated to the surface of the carrier, forming Cuδ+- VZr+ interfacial sites. The electrons around the zirconium vacancy of the CZ-ag-70 catalyst are in a completely delocalized state and Cu+ gains electrons which in turn produces Cuδ+- VZr+ interfacial sites.