Standard method validation is an important part of the quality management process in inspection and testing laboratories, and is the foundation for ensuring the accuracy of inspection and testing data. In this study, a method for determination of sulfonamides residues in water by UPLC-MS/MS was established.Verify the method from standard curve, linear range,quantification limit, precision, and method recovery rate. And the key experimental points of this method were analyzed and optimized. 17 kinds of sulfonamides have good linearity within the concentration range of 5.0 ng/mL-50 ng/mL. The correlation coefficient of calibration curve were more than 0.997. The detection limit of this method was 0.038 ng/mL. The average recovery rates of three spiked levels range from 74.6% to 105.6%, and the relative standard deviations were 0.89%～12.89%. The method could be used for quantitative determination of sulfonamides residues in water from aquaculture environment..