Trace acetone determination in breath can be regarded as a noninvasive method for diagnosis of diabetes. Here, a paper-based CL gas sensor combined with UiO-66 as the preconcentrator was established for sensitive detection of trace acetone in exhaled breath. UiO-66 with excellent adsorption performance and unique water stability was used for the adsorption and enrichment of acetone gas under high humidity conditions in exhaled breath. As acetone can remarkably increase the chemiluminescence (CL) of the 2,4-dinitrophenylhydrazine (DNPH)-potassium permanganate (KMnO4) system, a sensitive CL device based on a paper substrate for trace acetone detection was established and the detection limit was 0.03 ppm. The fabricated method was used to assess the content of trace acetone in exhaled breath with satisfactory recoveries of 90-110%. It is expected to realize the noninvasive determination of acetone for diabetic patients in exhaled breath.