Abstract: OBJECTIVE To optimize the optimal extraction process of Yangyin Runmu granules by using a multi-index comprehensive weighted scoring method combined with Box-Behnken design. METHODS Using the contents of puerarin, tangerine and isoferulic acid, ratio of dry extraction, total polysaccharides as comprehensive evaluation indicators, the weight coefficient of each evaluation index was determined by analytic entropy weight method-analytic hierarchy process. The single factor test and Box-Behnken design were used to investigate the influence of the water addition, time, and times of the water extraction process of Yangyin Runmu granules to optimize extraction process parameters. RESULTS According to the objective weight of each index determined by the mixed weighting method, the comprehensive scoring was performed, and the optimal extraction process condition of Yangyin Runmu granules was determined as adding 10 times of the amount of water, extracting 3 times, each time for 65 minutes. The verification test results show that compared with the measured value, the RSD of the predicted value was ≤ 3%. CONCLUSION The optimized extraction process has been verified to be stable, feasible and reproducible, which can provide experimental reference for the subsequent development and research of Yangyin Runmu granules.