Hierarchical hollow Au-loaded NiO hybrid microspheres have been synthesized with good uniformity by a surfactant-free hydrothermal route and subsequent heat treatment. This method requires high concentrations of a nickel precursor (0.2 M) and introduction of a trace amount of Au nanoparticles into the reaction system. The hierarchical hollow Au-loaded NiO hybrid microsphere comprises several nanorods and nanosheets. To demonstrate the usage of such hierarchical hybrid nanomaterials, a gas sensor has been fabricated from the as-synthesized Au-loaded NiO microspheres and investigated for acetone detection. The Au-loaded NiO sensor exhibits significantly improved sensing performances in terms of high sensitivity, low detection limit, better selectivity, rapid response, and good reproducibility in comparison with pure NiO. The effects of Au loading on the acetone-sensing properties of hierarchical NiO microspheres have been investigated.