Abstract: An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to determine residue of ribavirin and amantadine in chicken. Homogenized samples were extracted separately with a mixture of acetonitrile-1% trichloroacetic acid aqueous solution and a mixture of methanol-1% trichloroacetic acid aqueous solution, and then cleaned by solid phase extraction (SPE) . UPLC-MS/MS detection was performed using multiple reaction monitoring module. The quantification was obtained by utilizing the external standard method. Recoveries of metabolites of antiviral drugs ranged from 66.7% to 85.6% at fortified levels of 0.1 ~2.0μg/kg. The RSDs of the method were in the rang of 3.1% ~8.5%. The method was simple, effective and accurate. It could be applied to determine antiviral drugs residue in chicken.