Abstract: OBJECTIVE To establish a method for simultaneous determination of 5 cephalosporins residues in milk by UHPLC-MS/MS. METHODS Milk samples(about 5 g) were extracted by 10 mL Na₂EDTA-McIlvaine, centrifuged by a vortex, then get the middle-level clear liquid, the pH was adjusted to 8.5 by adding 0.1 mol·L^-1 NaOH solution, the supernatant were enriched and purified by HLB solid phase extraction column. The separation and analysis was performed on a Waters ACQUITY UPLC BEH(2.1 mm×50 mm, 1.7 μm) after enrichment and concentration. The mobile phase consisted of 0.1% formic acid and acetonitrile(gradient elution). Electrospray positive ion source was used for mass spectrometry detection by multiple reaction monitoring mode. RESULTS The five cephalosporins residues in milk had a good linear relationship within the quantitative limit of 20 times. The recoveries were 88.1%-114%, the RSD of repeatability test(n=6) was <6.55%, and the detection limit was 0.7-1.6 μg·kg^-1. CONCLUSION The method has good specificity, sensitivity and accuracy, and can be used for the simultaneous determination of cephalosporins residues in milk.