Objective: To optimize the preparation process for Haoqin-Huaban granules so as to provide experimental basis for the development and utilization of the compound. Methods: Taking the extraction rate of gentiopicroside from Gentiana macrophylla Pall as the observation index, L₉(3⁴)orthogonal test was used to investigate the amount of water, extraction time, and extraction frequency for optimizing the water extracting technology of the Haoqin-Huaban granules. Then the dry paste was used for the raw material, the ratio of the diluent (dextrin) and the concentration and dosage of the binder (ethanol) were investigated by single factor, and the particles were prepared. Results: The optimum water extraction process was A2B2C3, which indicated that the prescribed medicinal materials with 8 times water were extracted 1 h for 3 times. The extract was concentrated into paste, vacuum drying, pulverizing, mixing according to the ratio of 5:1, with ethanol, made of soft material, pelletizing, drying at 60 ℃ for granulation, in order to make Haoqin-Huaban granules. Conclusions The preparation process is reasonable and feasible, which provides experimental basis for the industrial production of Haoqin-Huaban granules.