Abstract: In this study, Ultra performance liquid chromatography-qiadrupole time-of-flight mass spectrometry was used to analyze the chemical components of the extract of Scutellariae radix, from which 26 flavonoids and flacomols were identified. The main active components including baicalin, scutellarin, wogonoside and wogonin were selected by network pharmacology oriented by drug and disease. The yields of these components were used as the evaluation indexes for extraction process optimization. The influence of process parameters on the indexes was investigated through definitive screening design, so as to establish the design space for the extraction of Scutellariae radix. The recommended operating space was as follows: the time and liquid-solid ratio of the first extraction was 35—45 min and 16—18, respectively; for the second extraction, the ethanol concentration was 35%—45%, the temperature was 78—82 ℃, the extraction time was 45 min and the liquid-solid ratio was 14—16. The extraction process was proved to be stable and reliable. This study has improved the correlation between process research and drug clinical practice, which provided ideas for actual quality improvement and process development.