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Lonicera japonica is a commonly used Chinese herbal medicine, but few studies have focused on its pesticide residues. In this study, a quick, easy, cheap, effective, rugged, safe (QuEChERS) pretreatment combined with gas chromatography-mass spectrometry (GC-MS) was established to determine 16 pesticides in L. japonica. Various factors including the type and volume of extraction solvent, times of ultrasound-assisted extraction, and type and weight of purifying agents were optimized. The established method showed good linearity with correlation coefficient (r) > 0.99 within the range of 0.01–5.0 mg·L−1, and average recoveries (AR) were 82.3%-102.5% at spiking levels of 0.01, 0.1, and 0.5 mg·kg−1 with relative standard deviations (RSD) of 0.43%-4.75%. Only bifenthrin and fenvalerate can be detected with maximum detected concentrations of 1.41 and 0.13 mg·kg−1. The results showed that the established method can be applied to detect pesticide residues in L. japonica with potential applications for other Chinese herbal medicines. [ABSTRACT FROM AUTHOR]