The acetone detection is of paramount significance for breath monitoring application, providing a new way for auxiliary medical diagnosis. However, the humidity dependence property hinders the promising applications of gas sensors in exhaled gas analysis. Herein, a surface engineering strategy coupling boron (B) doping and oxygen vacancy (O V) regulation was proposed to modulate the surface structures of NiO materials, leading to exhibiting satisfactory stability to humidity changes for acetone detection. The B-doped NiO with abundant O V (B-NiO-OVs) was facilely prepared by the redox reaction between Ni(NO 3) 2 and NaBH 4 at room temperature, followed by traditional annealing treatment, resulting in forming NiO materials with B content of 10 at% and O V of 37.3 %. As expected, B-NiO-OVs sensors showed high response value of 5.3 to 100 ppm acetone at 240 ºC, excellent selectivity and good repeatability. The improvement of acetone sensing performances is attributed to the regulation of electronic structure of Ni element. Most importantly, B-NiO-OVs sensor exhibits better anti-humidity property for acetone detection than other general metal oxides (ZnO and SnO 2). Additionally, this sensor also has a response value of 3.2 to 100 ppm acetone in 98 % relative humidity, and the response value to the simulated breath of diabetic patients is higher than 1.2, which can be significantly different from that of healthy people, extending the practical application in the auxiliary diagnosis of diabetes through exhalation. This work provides sound strategies to regulate the surface structure of metal oxides and fabricate high-performance metal oxides-based gas sensors.