A rapid method for the determination of zanamivir residues chicken tissues was developed using QuEChERS approach coupled with ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).After ultrasonically extracted with(0.2 mol/L) hydrochloric acid-methanol(1∶9),the supernate was purified by QuEChERS method.The separation was performed on a NUCLEOSHELL- HILIC(3.0 mm×100 mm，2.7 μm) column by gradient elution using a mobile phase consisted of 5 mmol/L ammonium acetate(containing 0.2% formic acid) and acetonitrile.The identification of zanamivir was carried out by MS/MS in positive electrospray ionization(ESI+) and multiple reaction monitoring(MRM) mode，and the quantification was performed by the external standard calibration method.The results showed that the calibration curves were linear in the range of 5-100 ng/mL with correlation coefficients(r) greater than 0.990.The limits of quantitation(LOQs，S/N=10) of this method were 10.0 μg/kg for the chicken muscle and liver.The average recoveries of zanamivir at three spiked levels of 10，20，100 μg/kg were in the range of 80.5%-88.7% with relative standard deviations(RSDs，n=6) of 7.3%-11.8%.The method was applied in the determination of zanamivir residues in practical chickens.The developed method is simple，accurate，rapid，sensitive and efficient,and could be applied in the determination of zanamivir residues in chicken tissues.