Residue field trials in cucumber were conducted for the safe use of a commercial formulation of cyproconazole·azoxystrobin 28% suspension concentrate (SC 294 g a.i. ha?1, three applications at a 7-day interval) in the year 2018, in China. To determine the residues of cyproconazole and azoxystrobin in cucumber, a quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was developed using high-performance liquid chromatography coupled with tandem mass spectrometry. This validated method was applied to analyze cucumber samples collected from 12 specified regions. At the 3-day interval to harvest, the highest residue (HR) of azoxystrobin was 0.150 mg kg?1, which was lower than the maximum residue limit (MRL; 0.5 mg kg?1) permitted in China, and the HR of cyproconazole was 0.084 mg kg?1, for which no MRL value has been set in China. The chronic risk quotient values of cyproconazole and azoxystrobin for Chinese adults at a 3-day interval to harvest were 2.56% and 13.72%, respectively. The acute risk quotient values of cyproconazole in cucumber were specified as 5.52% for children (1–6 years old) and 2.83% for the adults (>?18 years old) in China. These results indicate that cyproconazole·azoxystrobin 28% SC sprayed on cucumber at the pre-harvest interval of 3 days has no significant potential risk for Chinese consumers.