The development of highly potential electrocatalysts for acidic water electrolysis is particularly desirable for many energy-related processes. Herein, we demonstrated a versatile strategy to activate and stabilize RuO2-based electrocatalyst for acidic water splitting by a trace of Pt, where Pt plays an essential role in promoting oxygen evolution reaction (OER), and can simultaneously act as the active site for hydrogen evolution reaction (HER). Compared with pure Ru oxide nanosheet assemblies (Ru ONAs), the “5%Pt-containing” Ru ONAs (5%Pt-Ru ONAs) achieve much enhanced OER activity in 0.5 and 0.05 mol/L H2SO4, with much lower overpotentials of 227 and 234 mV at 10 mA cm−2, respectively. Experimental and theoretical analyses reveal that the atomically dispersed Pt incorporating into RuO2 lattice is conducive to increasing the concentration of O vacancies, which effectively enhances the interaction with reaction intermediate and thus lowers the energy barrier for the formation of OOH*. Moreover, benefited from the presence of Pt, the formation of RuO2 is more achievable when proper annealing is applied. In addition to OER, due to the presence of active Pt, the HER performance of 5%Pt-Ru ONAs can also be ensured, thereby realizing efficient acidic overall water splitting. Finally, the excellent activity can also be achieved without sacrificing stability. This work highlights an attractive strategy for designing active and stable RuO2-based electrocatalysts for acidic overall water splitting.