Polyimide nanofiber aerogels loaded with thymol blue and hydroxylamine sulfate (TB-HAS@PI NFAs) were synthesized and employed as a novel sensor for colorimetric detection of breath acetone (BrAce). The enhancement of 3D multi-level pore structure of TB-HAS@PI NFAs for sensing performance was elucidated through systematical characterization results. Because the designed sensing system relied on the specific reaction of HAS with acetone, TB-HAS@PI NFAs exhibited a more sensitive response ability to acetone, ensuring that the colorimetric sensing detection will not be interfered by other coexisting gas in exhaled breath. Moreover, the sensor demonstrated a rapid response, with color changes quantitatively measured within 30 s of exposure to acetone gas. Importantly, the feasibility and accuracy of established method were confirmed through comparison with GC–MS. This research provided a promising strategy for daily health management of healthy people and diabetics.