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Exploring cost-effective catalysts with high catalytic performance and long-term stability has always been a general concern for environment protection and energy conversion. Here, Au nanoparticles (NPs) embedded CuOx-CeO2 core/shell nanospheres (Au@CuOx-CeO2 CSNs) have been successfully prepared through a versatile one-pot method at ambient conditions. The spontaneous auto-redox reaction between HAuCl4 and Ce(OH)3 in aqueous solution triggered the self-assembly growth of micro-/nanostructural Au@CuOx-CeO2 CSNs. Meanwhile, the CuOx clusters in Au@CuOx-CeO2 CSNs are capable of improving the anti-sintering ability of Au NPs and providing synergistic catalysis benefits. As a result, the confined Au NPs exhibited extraordinary thermal stability even at a harsh thermal condition up to 700 °C. In addition, before and after the severe calcination process, Au@CuOx-CeO2 CSNs can exhibit enhanced catalytic activity and excellent recyclability towards the hydrogenation of p-nitrophenol compared to previously reported nanocatalysts. The synergistic catalysis path between Au/CuOx/CeO2 triphasic interfaces was revealed by density functional theory (DFT) calculations. The CuOx clusters around the embedded Au NPs can provide moderate adsorption strength of p-nitrophenol, while the adjacent CeO2-supported Au NPs can facilitate the hydrogen dissociation to form H* species, which contributes to achieve the efficient reduction of p-nitrophenol. This study opens up new possibilities for developing high-efficient and sintering-resistant micro-/nanostructural nanocatalysts by exploiting multiphasic systems.