A rapid screening and identification method for 45 veterinary drug residues in animal liver (pig liver， bovine liver， sheep liver， chicken liver， duck liver and goose liver) was established by using Prime HLB solid-phase extraction (SPE) purification and UHPLC-Q-Orbitrap high resolution mass spectrometry. The drugs were extracted with 0.2% formic acid and 80% acetonitrile aqueous solution， centrifuged， purified on Oasis Prime HLB solid phase extraction column， and redissolved after nitrogen blowing. The separation was performed on a Waters ACQUITY BEH C18 column (2.1 mm×100 mm， 1.7 μm). The mobile phase consisted of ammonium acetate (20 mmol/L) containing 0.1% formic acid and acetonitrile with gradient elution. The determination was performed in the first-stage full-scan/data-dependent two-stage scanmonitoring mode. The results showed that the linear relationships of 45 veterinary drugs were good in the concentration range of 1-2 000 μg/L， and the correlation coefficients were greater than 0.9959. The limits of detection were between 0.5 and 20 μg/kg， and the limits of quantification were between 2 and 50 μg/kg. The recoveries were 72.0%-112.2% with relative standard deviations (RSD) of 5.0%-10.5% at 3 supplemental levels. This method has the advantages of simple pretreatment， high throughput， accuracy and reliability， and is suitable for rapid screening and confirmative analysis of 45 veterinary drug residues in animal liver.