Abstract: An analytical method was developed for the determination of melamine and sulbactam in raw milk and liquid milk using hydrophilic interaction chromatography tandem mass spectrometry ( HILIC-MS/MS) .The samples were extracted with 2%acetic acid solution, and the protein was precipitated with acetonitrile subsequently.The separations of melamine and sulbactam were carried out on an Acquity UPLC BEH HILIC column using ammonium acetate solution-acetonitrile as mobile phase.The target compounds were carried out in the multiple reaction monitoring ( MRM) mode by employing the external standard method.The quantitation limit of mlamine was10 μg/kg.The recovery of melamine was 85.4% ¹02.5%, with the RSD of 3.10%⁶.55%.The quantitation limit of sulbactam was 1.0 μg/kg.The recovery of sulbactam was 86.1% ¹04.3%, with the RSD of2.35% ⁵.37%.With the advantages of convenience, sensitivity, good recoveries and repeatability, the method was suitable for the detection of melamine and sulbactam in raw milk and liquid milk.