Fangwen Jiuwei Decoction is a traditional Chinese medicine preparation for the treatment of pneumonia developed by Shenzhen Bao’an Chinese Medicine Hospital, which shows remarkable clinical responses. Qualitative and quantitative analyses of the main active compounds are crucial for the quality control of traditional Chinese medicine prescription in clinical application. In this study, we identified nine active compounds essential for the pharmacological effects of Fangwen Jiuwei Decoction based on the analysis of the Network Pharmacology and relevant literature. Moreover, these compounds can interact with several crucial drug targets in pneumonia based on molecular docking. We applied HPLC-MS/MS method was established these nine active ingredients’ qualitative and quantitative detections. The possible cleavage pathways of nine active components were determined based on secondary ions mass spectrometry. The results of HPLC-MS/MS were further validated, which show a satisfactory correlation coefficient (r>0.99), recovery rate (≥93.31%), repeatability rate (≤5.62%), stability (≤7.95%), intra-day precision (≤6.68%), and inter-day precision (≤9.78%). The limit of detection was as low as 0.01ng/mL. In this study, we estabilished an HPLC-MS/MS method to qualitatively and quantitatively analyze the chemical components in the Fangwen Jiuwei Decoction extract. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.