Antibiotics and sulfa drugs are widely used due to the function in preventing infections and curing diseases. These drugs cannot be completely metabolized in the organism, and cause environmental pollution in the food chain circulates, leading to continuous harm to human body. In recent years, more and more attention has been paid to the regulation of these drugs. Surface-enhanced Raman spectroscopy (SERS) based on localized surface plasmon resonance can enhance the Raman signal of molecules which adsorbed on the roughened metal surface, and the detection limit can reach single molecule level. Therefore, SERS-related technologies are widely used in the detection of trace substances, and the detection limit is mainly depended on the activity of the SERS substrate. In this study, the method of dealloying was used to prepare a uniform, adjustable pore size, and excellent performance nanoporous silver substrate and used to detect sulfadiazine and sulfacetamide, the detection limit reached 0.25μg/kg and 2μg/kg, which is far lower than 100μg/kg, The prescribed maximum residual amount of sulfa drugs in the Ministry of Agriculture of my country. And the Raman spectrum peak and the concentration of sulfa drugs showed a good linear relationship, the detection dynamic monitoring range is up to 106 orders of magnitude. The researched nanoporous silver can also be used for the detection of other pollutants, which has certain application value.