This study presents the development of a bicontinuous nanoreactor composed of multiscale defective RuO₂ nanomonomers (MD-RuO₂-BN) for acidic water oxidation. The unique bicontinuous structure of MD-RuO₂-BN provides abundant active sites and enhances mass transfer through cavity confinement. The presence of vacancies and grain boundaries in RuO₂ particles weakens the Ru-O interaction and inhibits the oxidation of lattice oxygen and the dissolution of high-valence Ru, leading to improved stability. Electrochemical tests show that MD-RuO₂-BN exhibits superior oxygen evolution reaction (OER) activity with a low overpotential of 196 mV at 10 mA cm⁻² and an ultralow degradation rate of 1.2 mV h⁻¹. A homemade proton-exchange membrane water electrolyzer (PEMWE) using MD-RuO₂-BN as the anode demonstrates high water splitting performance with a cell voltage of 1.64 V at 1 A cm⁻². Theoretical calculations and in-situ Raman spectra further elucidate the enhanced performance due to the synergistic effect of multiscale defects and protected active Ru sites. This work highlights the potential of Ru-based catalysts for practical applications in PEMWEs, offering a promising approach to replace expensive iridium-based materials.This study presents the development of a bicontinuous nanoreactor composed of multiscale defective RuO₂ nanomonomers (MD-RuO₂-BN) for acidic water oxidation. The unique bicontinuous structure of MD-RuO₂-BN provides abundant active sites and enhances mass transfer through cavity confinement. The presence of vacancies and grain boundaries in RuO₂ particles weakens the Ru-O interaction and inhibits the oxidation of lattice oxygen and the dissolution of high-valence Ru, leading to improved stability. Electrochemical tests show that MD-RuO₂-BN exhibits superior oxygen evolution reaction (OER) activity with a low overpotential of 196 mV at 10 mA cm⁻² and an ultralow degradation rate of 1.2 mV h⁻¹. A homemade proton-exchange membrane water electrolyzer (PEMWE) using MD-RuO₂-BN as the anode demonstrates high water splitting performance with a cell voltage of 1.64 V at 1 A cm⁻². Theoretical calculations and in-situ Raman spectra further elucidate the enhanced performance due to the synergistic effect of multiscale defects and protected active Ru sites. This work highlights the potential of Ru-based catalysts for practical applications in PEMWEs, offering a promising approach to replace expensive iridium-based materials.