The electrocatalytic ethanol oxidation reaction (EOR) is a critical component of direct ethanol fuel cells, while its reactivity, stability, and selectivity toward C 1 products are severely hindered by the poisoning effect of CO species on the surface of noble-metal catalysts. In this work, we developed a hybrid material of palladium nanoparticles and nickel single-atom catalysts (Pd NPs@Ni SAC) for efficient EOR. The Pd nanoparticles catalyze the breaking of carbon-carbon bonds of ethanol, while the adsorbed CO intermediates are removed by the Ni single-atom catalyst. The Pd NPs@Ni SAC structure exhibits outstanding EOR performances, including high mass activity, good selectivities of C 1 products, and excellent electrocatalytic stability. Our work suggests an attractive perspective of utilizing single-atom electrocatalysts for ethanol oxidation. A Pd nanoparticle@Ni single-atomic catalyst (SAC) was developed for electrocatalytic ethanol oxidation. The Pd nanoparticles served as catalytic sites of ethanol, and the produced CO species adsorbed on Pd were electrochemically oxidized by Ni SAC.