Abstract: OBJECTIVE To optimize the water extraction process of compound Honghuang buccal tablets. METHODS The water addition ratio, extraction time and extraction frequency were selected as the investigate factors, and the orthogonal test was carried out with the total polysaccharides content and extraction yield as the inspection indexes. A quadratic regression model of total polysaccharide content and extraction yield was established by Minitab 18.0 software, further multi-objective genetic algorithm was used to optimize the orthogonal test results and determine the optimal extraction process of compound Honghuang buccal tablets. RESULTS The optimal extraction process was as follows:10 times the amount of water, reflux extraction 3 times, 2.94 h for each time. CONCLUSION The optimized extraction process is stable and feasible, and the rates of extracting effective ingredients is high. It can be used to extract compound Honghuang buccal tablets.