Realizing stable and efficient overall water splitting is highly desirable for sustainable and efficient hydrogen production yet challenging because of the rapid deactivation of electrocatalysts during the acidic oxygen evolution process. Here, we report that the single-site Pt-doped RuO 2 hollow nanospheres (SS Pt-RuO 2 HNSs) with interstitial C can serve as highly active and stable electrocatalysts for overall water splitting in 0.5 M H 2 SO 4 . The performance toward overall water splitting have surpassed most of the reported catalysts. Impressively, the SS Pt-RuO 2 HNSs exhibit promising stability in polymer electrolyte membrane electrolyzer at 100 mA cm −2 during continuous operation for 100 hours. Detailed experiments reveal that the interstitial C can elongate Ru-O and Pt-O bonds, and the presence of SS Pt can readily vary the electronic properties of RuO 2 and improve the OER activity by reducing the energy barriers and enhancing the dissociation energy of * O species.