An approach based on surface-enhanced Raman spectroscopy (SERS) was developed to rapidly detect the diethylstilbestrol residues in duck meat in this study. Firstly, the single factor analysis method was adopted to determine the optimal amounts of sodium citrate, Au nanoparticles, duck meat extract containing diethylstilbestrol and magnesium sulfate solution, as well as the optimal measurement time. The quantitative analysis model for the detection of DES residues in duck meat was established after a simple pretreatment for duck meat was done. Thereafter, based on the basis of the above study, the linear equation with minimum detection concentration of 0.5 mg/L was established using diethylstilbestrol concentrations in duck meat extract and Raman intensities at 819 cm^-1. Furthermore, the R² value for prediction set was 0.969 0, and the root mean square error for prediction (RMSEP) with average recovery of 83%～133% was 0.728 1 mg/L. The experimental results indicated that the method adopted in the present study could be applied to detect DES residues in duck meat.