The invention provides a UPLC-MSMS detection method for residue of 19 types of sulfonamides in farmed fish by a C18-based ASE method, and belongs to the technical field of veterinary drug residue detection. By adding the sample, diatomite and C18 filler into the extraction pond in layers, the ASE method can be used for simultaneous extraction and purification, and the experimental method can be simplified. On the basis of the sample pretreatment technology, the introduction of low-temperature freezing technology to assist the purification effect of ASE method on the sample can effectively remove the complex biological matrix (such as polar fat), significantly reduce the matrix effect and improve the sensitivity of the method. Combining with the UPLC-MSMS, the detection of residue of a plurality of types of sulfonamides in farmed fish is successfully applied, and the detection limit of the established method has been significantly reduced to 2-10 times than the existing standard method.The detection method provided by the invention is simple and efficient, high in sensitivity and high in the degree of automation, and is suitable for accurate qualitative and quantitative analysis and detection of large quantity of veterinary drug detection samples.