Designing electrocatalysts that are both highly efficient and durable is crucial for the industrial implementation of alkaline electrocatalytic hydrogen production technologies. A limitation of the current Ru-based catalysts is that the water dissociation energy barrier tends to be too high. Here, the electronic structure of ruthenium nanoclusters (Ru NCs) is modulated by single atom Ni-N4 sites leading to leading to lowering of the water dissociation barrier. X-ray absorption fine structure spectrum confirms that Ru NCs are stably anchored on the carbon support through the formation of Ru-N bonds, significantly enhancing catalytic stability. The resulting Ru/Ni-N4C-300 catalyst shows excellent catalytic activity toward alkaline hydrogen evolution reaction with a low overpotential of 15.0 mV at 10 mA cm−2 together with robust durability. An anion exchange membrane water electrolyzer employing Ru/Ni-N4C-300 can be stably operated under 500 mA cm−2 for over 1370 h, surpassing the parameters required for industrialization. Theoretical calculation indicates the single atom Ni-N4 sites in Ru/Ni-N4C-300 optimize the electron distribution of Ru NCs, thereby reducing the Gibbs free energy of intermediates species in water dissociation process.