Objective To optimize the extraction process for compound Hongjingshen Pill. Methods The survival time of normobaric hypoxia-tolerant mice and acute cerebral ischemic-hypoxic mice was used as an assess⁃ment index to perform the pharmacodynamic screening among three process routes for compound Hongjingshen Pill. For the selected process route，taking the content of salidroside and total polysaccharides and dry extract yield as as⁃sessment indices，and the solid/liquid ratio，soaking time，extraction time，and extraction times as the factors to consider，single-factor experiments and response surface methodology (RSM）were used to optimize the water ex⁃traction process for three decoction pieces: Rhodiola rosea，Ophiopogon japonicus，and Dendrobium nobile. Results The optimal extraction process for compound Hongjingshen Pill was as follows: Crush Panax ginseng and Salvia miltiorrhiza into powder for later use；soak Rhodiola rosea，Ophiopogon japonicus，and Dendrobium nobile in water for 60 minutes；decoct the ingredients twice with a solid/liquid ratio of 1:18 and a decoction time of 85 min. Conclu-sion The optimal extraction process of compound Hongjingshen Pill was obtained，which provides an experimental basis and technical support for its development as an healthcare product for improving hypoxia tolerance.