For environmental catalysis, a central topic is the design of high-performance catalysts and advanced mechanism studies. In the case of the removal of flue gas pollutants from coal-fired power plants, highly selective nanoreactors have been widely utilized together with plasma discharge characteristics, such as the catalytic oxidation of NO. Herein, a novel reactor with a three-dimensional hollow structure of TiO 2 confining Co 3 O 4 nanoclusters (Co 3 O 4 /TiO 2 -3DHS) has been developed for plasma-catalytic oxidation of NO, whose performance was compared with that of the commercial TiO 2 confining Co 3 O 4 cluster (Co 3 O 4 /TiO 2 ). Specifically, Co 3 O 4 /TiO 2 -3DHS presented a higher efficiency (almost 100%) within lower peak−peak voltage (V P−P ). More importantly, the NO oxidation efficiency was between 91.5 and 94.5% after a long time of testing, indicating that Co 3 O 4 /TiO 2 -3DHS exhibits more robust sulfur and water tolerance. Density functional theory calculations revealed that such impressive performance originates from the unique cluster-support effect, which changes the distribution of the active sites on the catalyst surface, resulting in the selective adsorption of flue gas. This investigation provides a new strategy for constructing a three-dimensional hollow nanoreactor for the plasma-catalytic process.