Herein, a new mechanism involving Lewis acid-oxygen vacancy interfacial synergistic catalysis for aniline N,N-diethylation with ethanol was proposed, and the SO42-/Ce0.84Zr0.16O2-WO3-ZrO2 catalyst (SCWZ) with both Lewis acid sites and oxygen vacancies was synthesized by the hydrothermal method, which shows better catalytic activity than the reported solid acidic catalysts. Besides, the SO42-/ZrO2 (SZ) and SO42-/WO3-ZrO2 (SWZ) catalysts were also prepared and compared with SCWZ to investigate the synergistic effect of each component. The SO42-and WO3 mainly generate Lewis acid by bonding with ZrO2, which is beneficial for the fracture of the N-H bond in aniline. The Ce0.84Zr0.16O2 solid solution mainly plays a vital role in generating the oxygen vacancies as the interface active species, which can participate in stripping-OH from ethanol, then the carbocation will also be released, which only needs 1.3805 kcal/mol energy, calculated by density functional theory (DFT), to be input. In comparison, the traditional reaction mechanism needs the Br?nsted acidic sites to promote the protonation of ethanol, then dehydration and subsequent formation of carbocation followed, and 108.6846 kcal/mol energy needs to be input, which is far higher than that of the new mechanism. The apparent activation energy (Ea) over SCWZ was measured by experiment to be 34.09 kJ/mol, which is much lower than that of SWZ (47.10 kJ/mol) and SZ (54.37 kJ/mol), illustrating comparatively preferable kinetics for SCWZ than that of SWZ and SZ. Besides, the conversion of aniline and selectivity to N,N-diethylaniline over SCWZ reach almost 100％and 73％, respectively. The SCWZ can be renewed for 4 times without rapid deactivation, and the longevity of SCWZ is longer than that of SWZ and SZ, as the loaded SO42- and tetragonal ZrO2 are stabilized by Ce0.84Zr0.16O2 and WO3, respectively.