stemming from high overpotential due to the sluggish four-electron transfer of anodic oxygen evolution reaction (OER). [2] To solve above problems, the novel idea of hybrid water electrolysis has been proposed, in which thermodynamically favorable organic reforming reactions are selected to replace the OER. [3] Consequently, organic biomass can be oxidized to high value-added products at low potentials, realizing decoupled hydrogen evolution from water splitting. Ethanol (CH 3 CH 2 OH) is a clean, economical, and sustainable energy source which can be easily obtained, stored, and transported. [4] Therefore, anodic ethanol electro-oxidation reaction (EOR) has been considered as a promising strategy to replace oxygen evolution reaction (OER), reducing the energy consumption for hydrogen generation and co-producing high-value-added chemicals.Normally, platinum group metals (PGMs) have the best catalytic activity as EOR catalysts. [5,6] But the PGMs have some drawbacks such as high cost. [7] The reaction intermediates are easily adsorbed on the catalysts, poisoning the active sites, and causing the rapid decay of EOR. [8,9] Furthermore, serious security issue due to mixing of O 2 and H 2 could not be avoided. [2] However, these problems will be resolved if non-platinum group metals (NPGMs) are used as catalyst. [10][11][12][13][14] Similar with PGMs, the EOR on NPGMs also encounter with the sluggish kinetics of the multi-electron transfer process. [15] Thus, it is important to develop cost-effective electrochemical catalyst with high reactivity for EOR. [16] Recently, abundant Ni-based EOR catalysts have been reported. [17,18] However, the catalytic mechanism of these Nibased electrocatalysts still remains uncertain. It has become a consensus that Ni species with high valence are active sites for OER. [19,20] However, this does not seem to be the case with EOR. So the determination of the active sites of Ni-based catalysts for EOR is a problem to be solved. In order to improve the catalytic activity, many approaches have been conducted, such as vacancy engineering, [21,22] heteroatom doping, [23,24] crystalline phase transforming, [25,26] and heterostructure constructing. [27,28] However, the effect of above approaches on the modulation of electronic structure and coordination environment of Ni sites remains uncertain. [4] Thus, it is important to determine the It is a good idea for efficient production of hydrogen to use ethanol oxidation reaction (EOR) in place of oxygen evolution reaction (OER) in water electrolysis process. Ni-based non-precious electrocatalysts are widely used in the conversion of ethanol to acetic acid. Here, different selenide heterostructures (NiCoSe, NiFeSe, and NiCuSe) are prepared in which Ni sites are regulated by transition metal. The valence state of Ni is NiCuSe < NiCoSe < NiFeSe in the three heterojunctions. NiCoSe shows the optimized charge distribution of Ni sites and outstanding catalytic activity. The effective modulations lead to optimized d-band center and facilitates both adsor...