Isoprene is a typical biomarker for nonalcoholic fatty liver disease (NAFLD) and can be used for early screening in breath diagnosis. In this study, a simple hydrothermal synthesis of flower-like Cr2O3-doped In2O3 nanorods clusters materials for ultra-low isoprene detection was reported. This special flower-like nanorods clusters structure has the large specific surface area and the Cr2O3 doping improves in the distribution of different oxygen components, crystallite size, and carrier concentration, which synthetically contributes to the enhanced isoprene sensing performance. The results show that among all the sensors, the 1 wt% Cr2O3-doped In2O3 sensor exhibits reliable ppb-level detection ability with a concentration less than 5 ppb. Meanwhile, the sensor shows good long-term stability for 4 weeks and considerable selectivity over other common breathing gases (benzene, acetone, octane, pentane, ethanol, ammonia, and nitrogen dioxide). Furthermore, the sensor has good humidity resistance under different ambient humidity (0–92% RH). Thus, we believe the sensor based on the flower-like Cr2O3-doped In2O3 nanorods clusters has a potential application value for the detection of trace isoprene in breath analysis. The flower-like Cr2O3-doped In2O3 nanorods clusters materials for ultra-low isoprene detection are synthesized via a facile hydrothermal method. Display omitted