Gas sensors for acetone detection have received considerable attention because acetone has a significant influence on both the environment and human health, e.g., it is flammable and toxic and may be related to blood glucose levels. However, achieving high sensitivity and selectivity at low concentrations is still a great challenge to date. Here, we report a unique chemiresistive gas sensor for acetone detection, which is composed of In 2 O 3 nanofibers loaded with a porous Co-based zeolitic imidazolate framework (ZIF-67)-derived Co 3 O 4 cage prepared by simple electrospinning and solvothermal methods. The ZIF-67derived oxide cage/nanofiber Co 3 O 4 /In 2 O 3 heterostructure has abundant reversible active adsorption/reaction sites and a type-I heterojunction, resulting in an ultrasensitive response of 954−50 ppm acetone at 300 °C. In addition, it demonstrates a low detection limit of 18.8 ppb, a fast response time of 4 s, good selectivity and repeatability, acceptable humidity interference, and long-term stability. With such excellent sensing performance to acetone, our chemiresistive gas sensor could be potentially applied for environmental monitoring and early diagnosis of diabetes.