This study presents a bicontinuous nanoreactor composed of multiscale defective RuO₂ nanomonomers (MD-RuO₂-BN) for acidic water oxidation. The unique bicontinuous structure provides abundant active sites and enhances mass transfer through cavity confinement. The presence of vacancies and grain boundaries in MD-RuO₂-BN leads to low-coordination Ru atoms and weakened Ru-O interactions, inhibiting lattice oxygen oxidation and high-valence Ru dissolution. The MD-RuO₂-BN exhibits hyper water oxidation activity (196 mV @ 10 mA cm⁻²) and an ultralow degradation rate of 1.2 mV h⁻¹. A homemade PEMWE using MD-RuO₂-BN as anode achieves high water splitting performance (1.64 V @ 1 A cm⁻²). Theoretical calculations and in-situ Raman spectra reveal the electronic structure and water oxidation mechanism, showing the synergistic effect of multiscale defects and protected active Ru sites. The bicontinuous nanoreactor design enhances the performance of RuO₂-based catalysts, offering a promising solution for practical applications in PEMWEs. The study highlights the importance of structural design and defect engineering in improving the activity and stability of Ru-based catalysts for oxygen evolution reactions in acidic environments.This study presents a bicontinuous nanoreactor composed of multiscale defective RuO₂ nanomonomers (MD-RuO₂-BN) for acidic water oxidation. The unique bicontinuous structure provides abundant active sites and enhances mass transfer through cavity confinement. The presence of vacancies and grain boundaries in MD-RuO₂-BN leads to low-coordination Ru atoms and weakened Ru-O interactions, inhibiting lattice oxygen oxidation and high-valence Ru dissolution. The MD-RuO₂-BN exhibits hyper water oxidation activity (196 mV @ 10 mA cm⁻²) and an ultralow degradation rate of 1.2 mV h⁻¹. A homemade PEMWE using MD-RuO₂-BN as anode achieves high water splitting performance (1.64 V @ 1 A cm⁻²). Theoretical calculations and in-situ Raman spectra reveal the electronic structure and water oxidation mechanism, showing the synergistic effect of multiscale defects and protected active Ru sites. The bicontinuous nanoreactor design enhances the performance of RuO₂-based catalysts, offering a promising solution for practical applications in PEMWEs. The study highlights the importance of structural design and defect engineering in improving the activity and stability of Ru-based catalysts for oxygen evolution reactions in acidic environments.