TiO2 hollow spheres modified with spatially separated Ag species and RuO2 cocatalysts have been prepared via an alkoxide hydrolysis–precipitation method and a facile impregnation method. High-resolution transmission electron microscopy studies indicate that Ag species and RuO2 co-located on the inner and outer surface of TiO2 hollow spheres, respectively. The resultant catalysts show significantly enhanced activity in photocatalytic hydrogen production under simulated sunlight attributed to spatially separated Ag species and RuO2 cocatalysts on TiO2 hollow spheres, which results in the efficient separation and transportation of photogenerated charge carriers.