A novel two-dimensionalhydrophilicinteraction chromatography/reversed phase liquid chromatography-tandem mass spectrometry system was developed to analyzeseven categories of antibiotics residues in dairy products.The seven categories were β-lactams,tetracyclines,macrolides,aminoglycosides,amphenicols,quinolones,and sulphonamides,and involved 20 antibiotics.Samples of milk powder or milk samples were extracted by mixed matrix solidphase dispersion using C18 and CN material.The analytes were eluted by acetonitrile and water,and were dried with rotary evaporation.Finally,the residues were dissolved with mobile phase and then analyzed.Sample pretreatment conditions,chromatographic and mass spectrometric parameters were optimized.Twenty analytes showed good linearities with correlation coefficients of 0.9945~0.9998.The limits of detection and quantification for milk powder and milk samples were 0.10~2.40 μg/kg and 0.33~7.92 μg/kg,respectively.The proposed method has been applied to the determination of antibiotics residues in milk powder and milk samples.