Abstract: A detection method using UHPLC-MS/MS was established for the determination of 53 prohibited veterinary drug residues in goat horns, including 16 tranquilizers, 14 β-agonists, chloramphenicol, 4 fluoroquinolones, 7 nitroimidazoles, 3 quinoxalines, and 8 other compounds. Samples were extracted using salting-out assisted liquid-liquid extraction (SALLE). A Zorbax Eclipse Plus C18 column (1.8 μm, 3.0 mm × 150 mm, Agilent) was used with 0.1% formic acid solution-acetonitrile as the mobile phase for gradient elution. Detection was performed in positive and negative electrospray ionization modes using multiple reaction monitoring (MRM). All 53 analytes showed good linearity within their respective concentration ranges, with correlation coefficients above 0.99. The average recoveries at three spiked levels ranged from 70.4% to 118.7%, with relative standard deviations (RSDs) ranging from 0.69% to 12.07%. The limits of detection (LODs) ranged from 0.1 to 50 μg·kg^-1, and the limits of quantitation (LOQs) ranged from 0.2 to 100 μg·kg^-1. This method has been applied to the determination of real samples.