Sensitive and selective detection of acetone in human exhaled breath plays an important role in the diagnosis of diabetes. However, obtaining a reliable response to ppb levels of acetone and avoiding cross-sensitivity due to the large amount of moisture in exhaled breath are still great challenges. In this work, a type of acetone sensor with ultrahigh sensitivity and moisture resistance is reported. Electrospun In 2 O 3 nanowires with a controllable Pt core (Pt@In 2 O 3 core-shell nanowires) are designed and prepared as sensitive layers. A mesoporous silica molecular sieve is further integrated as the moisture filter layer. The Pt@In 2 O 3 core-shell nanowire-based sensor exhibits a highly improved response compared with a sensor based on pure In 2 O 3 nanowires due to the probable increase in surface resistance and the introduction of p-n junctions after rational design of the structure. In addition, a good performance in terms of the fast dynamic process, selectivity and long-term stability is also achieved, and the detection limit can be as low as 10 ppb, which is much lower than the concentration level of 1.8 ppm in the exhaled breath of diabetic patients. The influence of the large amount of moisture is greatly weakened by using the molecular sieve as a moisture filter layer, leading to much improved sensitivity in clinical sample detection among healthy and diabetic patients. Based on the optimized composite structure of the Pt@In 2 O 3 core-shell nanowire sensor and moisture filter layer, a simple portable sensing prototype is successfully fabricated. The reported Pt@In 2 O 3 core-shell nanowires and the acetone sensing approach open up a new opportunity for a simple, inexpensive, and noninvasive diagnosis of diabetes.