OBJECTIVE： To optimize the extraction technology of Danzhi xiaoyao powder. METHODS： The medicinal powder in the formula of Danzhi xiaoyao powder was extracted by using the heating reflux method. Box-Behnken Design （BBD） response surface methodology （RSM） was adopted for trial design with ethanol volume fraction， extraction time and ratio of water to material （V/m） as factors by using comprehensive scores of geniposide， paeoniflorin and paeonol as evaluation indexes. After mathematical model and objective function were obtained， genetic algorithm and direct search method were used to obtain the optimum ranges and value of extraction process parameters. RESULTS： The optimal extraction technology of three indexes in Danzhi xiaoyao powder included 60.8％ ethanol， extraction time of 3.1 h， water-material ratio of 15.72 ∶ 1 （mL/g）. There was no statistical significance in the difference of comprehensive scores by BBD RSM alone or combined with genetic algorithm and direct search method （P＞0.05）. CONCLUSIONS： The technology can be used for the extraction of index from Danzhi xiaoyao powder. BBD-RSM combined with genetic algorithm and direct search method has certain superiority in optimizing the extraction process of TCM.