Abstract: Objective : An analytical method based on the gas chromatography-mass spectrometric had been developed for the determination of nonylpbenol in milk powder. Method:Firstly,selecting the appropriate extraction and purification cartridge by the contrast experiment,then,by using the chromatographic peak area as response values,the temperature,time and the dosage of silylation reagent involved in the derivatization procedure were optimized by central composite design. Results:Acetonitrile was used as extractant and protein precipitator,the solid-phase extraction was conducted on a florisil extraction cartridge,and the silylation reagent was trimethyl chlorosilance with 1% trimethyl chlorosilane. Under the temperature of 72 ℃,with the dosage of silylation reagent of 215 μL,after a reaction time of 27 min,the derivatization of nonylpbenol reach the best result.Conclusions:Under the optimal conditions,the limit detection of nonylpbenol was 24.0 μg/kg,linearity range was 10.70~1369 ng/m L,and the recoveries ranged from 90.6% to 105.2% with a relative standard deviations of2.7%. This method is accurate,sensitive,with small sample matrix interference,and applicable to the determination of nonylpbenol in milk powder.