The rapid detection of acetone gas plays a crucial role in controlling air pollution and realizing the non-invasive diagnosis of diabetes. Here, the In-doped Fe2O3 spindles derived from metal-organic framework (MOF) were prepared by hydrothermal method, and the efficient detection of acetone gas was realized. Due to the In3+ doping, the surface of the In-doped Fe2O3 spindles nanomaterials is covered with cracks. The BET surface area also increased from 19.755 m2/g−1 to 30.872 m2/g−1, which provides more active sites for the adsorption of oxygen molecules and target gases, thereby enhancing its gas sensing performance. As the results show, the In-doped Fe2O3-based gas sensor has a response of 31.7 to 100 ppm acetone gas at 320 °C, and the response recovery time is 1 s/1 s. Compared with the pure Fe2O3-based gas sensor, the In-doped Fe2O3-based gas sensor maintains fast response-recovery while exhibiting excellent selectivity for acetone gas. Therefore, the In-doped Fe2O3 gas sensors have broad application prospects in acetone gas detection.