Developing low cost and highly active catalysts for the oxygen evolution reaction (OER) in an acidic medium is urgently indispensable for proton exchange membrane water electrolyzers (PEMWEs). Herein, we have prepared ultra-thin RuO 2 nanosheets (RuO 2 NSs) using a simple molten salt method. The as-prepared RuO 2 NSs with a thickness of 1-2 nm possess abundant defects. Toward the OER, the RuO 2 NSs achieve an extremely low overpotential of 199 mV at a current density of 10 mA cm geo −2 with a loading of 125 μg cm geo −2 . Furthermore, the RuO 2 NSs exhibit specific and mass activities of up to 0.89 mA cm oxide −2 and 0.52 A mg Ru −1 at 1.46 V vs. RHE, which are 14.9 and 80.6 times enhanced in specific and mass activity as compared to the commercial RuO 2 nanoparticles, respectively. In a homemade PEMWE, with RuO 2 NSs as the OER catalyst, the electrolyzer achieves a current density of 0.93 A cm −2 at a cell voltage of 1.65 V without iR drop correction, which is 3 times larger than that of the commercial RuO 2 catalyst (0.31 A cm −2 ). Density functional theory calculations indicate that the Ru vacancy on the RuO 2 NS surfaces significantly weakens the binding energy of O* with respect to that of OOH*, which decreases the energy cost in the transformation from O* to OOH*, and thus dramatically enhances the OER performance. The unique defect-rich structure and outstanding performance demonstrate that the RuO 2 NSs possess great potential for developing high-performance PEMWEs. A Ru vacancy decreases the energy barrier from O* to OOH*, thus dramatically enhancing the OER performance of defect-rich RuO 2 nanosheets.