A versatile nanoprobe for acetone vapor was designed and fabricated. It is based on the use of gold-doped three-dimensional (3D) hierarchical porous zinc oxide microspheres (Au/ZnO HPMSs). The nanoprobe was synthesized by annealing zinc hydroxide carbonate precursor (obtained by a hydrothermal method) doped with gold nanoparticles. The resulting products possess a 3D open framework structure built of 2D porous nanosheets with a nanoporous wormhole-like shape. The microspheres doped with 0.5mol% gold display a good selectivity towards acetone. The conductometric nanoprobe, typically operated at a voltage of 5V, can detect sub-ppm levels of acetone, and the detection limit is as low as 0.2ppm. The response (at a level of up to 100ppm of acetone at 325°C) was high (74 ± 1.9), and the response and recovery time are 6 and 3s, respectively. This superior performance is ascribed (a) to the hierarchical porous ZnO architecture that warrants a large surface area; and (b) to the presence of gold nanoparticles that facilitate the chemisorption and dissociation of gas molecules. Graphical abstract Gold-doped 3D hierarchical porous ZnO microspheres (Au/ZnO HPMSs) architectures assembled by interconnected 2D porous nanosheets structures. The resistive sensor using these Au/ZnO HPMSs demonstrates outstanding acetone vapor sensing behaviors and 0.2ppm detection limits.