Abstract: OBJECTIVE To optimize the best decocting process of Shilishu granules. METHODS Taking hypericin, hesperidin, puerarin, total polysaccharide yield and dry extract yield as the indexes, the weight distribution and comprehensive score of the measured data were carried out by analytic hierarchy process(AHP), criteria importance through inter-criteria correlation(CRITIC) and AHP-CRITIC mixed weighting method. The results of single weighting method and mixed weighting method were compared, and the Box-Behnken response surface test was carried out with the comprehensive score as the response value to optimize the decoction process and verify it. RESULTS The AHP-CRITIC mixed weighting method was more scientific, reasonable and comprehensive than the single weighting method. The optimal decocting process was to add 11 times the amount of water and decoct 3 times for 80 min each time. CONCLUSION AHP-CRITIC method can be used to determine the weight of multiple indexes in the decocting process of Shilishu granules. The validation test shows that the optimized decocting process is stable and feasible, and can be used in industrial production.