Selective and quantitative detections of an acetone gas by semiconductor gas sensors have attracted much attention owing to their noninvasiveness. However, their low selectivity and high working temperature limit the range of their practical use. In this work, we report indium−tin−zinc ternary amorphous oxide (ITZO) nanoparticles for acetone sensing. ITZO nanoparticles are prepared by a liquid phase method. The size of the ITZO nanoparticle is ca. 150 nm, and ITZO has an amorphous structure with a uniform distribution of In, Sn, and Zn. ITZO shows the selective sensor responses (R air /R gas = 51) to an acetone gas (10 ppm) at 250 °C. From operando DRIFTS observations, acetone molecules adsorb on Lewis acid sites and they are converted into carboxylate intermediates, followed by their decomposition during acetone detection. Repetitive redox cycles are confirmed by operando UV−vis observations. The similarity of the surface reaction mechanism between acetone and ethanol is suggested, which affects the selectivity of the gas sensors.