A simple,sensitive and accurate method consisted of ultrasound assisted extraction （UAE） coupled with QuEChERS and high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS） was developed for the determination of quinocetone （QCT） in liver tissue of fish.The extraction solvent,extraction time and solid sorbent were optimized.The liver tissues were extracted with ethyl acetate,and purified by the mixture of primary secondary amine（PSA） and graphitized carbon blacks（GCB）.The identification of QCT were achieved by using electrospray ionization in positive ion mode （ESI+） under multiple reaction monitoring（MRM） mode.The analysis of QCT was performed by the external standard method.The calibration curve was linear in the range of 5-100 μg/L with a correlation coefficient of 0.998 8.The limit of detection（LOD,S/N=3） was 5 μg/kg and the limit of quantitation（LOQ,S/N=10） was 10 μg/kg.The method was applied in the determination of QCT in the hybrid snakehead liver tissues,and the recoveries at three spiked levels of 10,25,100 μg/kg ranged from 98.6% to 110.0% with relative standard deviations （RSDs,n=3） of 5.9%-10.1%.The proposed method was applied in the final residue detection after feeding Hybrid Snakehead with feed containing 75 mg/kg QCT for 60 consecutive days.The result showed that QCT was depleted quite fast in hybrid snakehead,and the elimination half life time of snakehead was 2.31 h.Therefore,it could be concluded that QCT was safe in feeding Hybrid Snakehead.