Abstract: OBJECTIVE To optimize the extraction process for Cupai mixture by orthogonal design. METHODS Orthogonal design method L9(43) was applied to optimization of extraction process for Cupai mixture, and the contents of 2,3,5,4-tetrahydroxy toluylene-2-O-β-D-glucoside in the extract and the percentage of extract were used as indices for evaluation of the extraction process. RESULTS The optimal extraction process was characterized as follows. The water used was 10 times the amount of crude drugs. The crude drug should be immersed for 22 h and decoction should be repeated for three times, each of which lasted for 2 h. The results of optimized extraction process were validated for three times. The mean value for the extract percentage were 61.23%-62.04%, and the effective component 2,3,5,4-tetrahydroxy toluylene-2-O-β-D-glucoside were 0.48-0.58 mg·mL^-1. CONCLUSION The optimized extraction method is reasonable and feasible.