Abstract: A method of QuEChERS-UPLC-MS/MS was proposed for rapid determination of 22 sulfonamide residues in fish. The sample was extracted with a mixture of acetonitrile with 0.1% (φ) formic,and the extract was purified by QuEChERS method. The target analytes were separated on an Agilent ZORBAX Eclipse Plus C18 column,using a mixture of methanol and 0.1% (φ) formic solution as mobile phase for gradient elution. ESI+ and schedule MRM were adopted in MS/MS,quantification was carried out by the internal standards method. The linear ranges of sulfanilamide,sulfaquinoxaline and sulfanitran were 0.5-50 μg·L-1 with detection limits (3S/N) of 0.5 μg·L-1. For the other 19 sulfonamides,the detection limits (3S/N) were 0.1 μg·L-1 and the linear ranges were 0.1-50 μg·L-1. The recovery rate measured by standard addition method was in the range of 78.2%-118%,with RSD′s (n=6) in the range of 3.4%-19%.The method was used for rapid determination of 22 sulfonamide residues in fish,giving results in agreement with those obtained by the standard method.