Aim and Objective. This study was designed to explore the active compounds and significant pathways of Huaiqihuang Granule (HQHG) for treating immune thrombocytopenia (ITP) using LC-MS/MS analysis, molecular docking, and network pharmacology. Materials and Methods. Compounds of HQHG were scanned by LC-MS/MS, and the target profiles of compounds were identified based on SwissTarget Prediction. ITP target proteins were collected from various databases. Then, KEGG pathway and GO enrichment analyses were performed to explore the signaling pathways related to HQHG for ITP. The PPI and drug-herbs-compounds-targets-pathways network were constructed using Cytoscape 3.7.2. Finally, Discovery studio software was used to confirm the key targets and active compounds from HQHG. Results. A total of 187 interacting targets of 19 potentially active compounds in HQHG and 3837 ITP-related targets were collected. Then, 187 intersection targets were obtained. A total of 20 key targets including EGFR, CASP3, TNF, STAT3, and ERBB2 were identified through PPI network analysis. These targets were mainly focused on the biological processes of positive regulation of protein phosphorylation, cellular response to organonitrogen compound, and cellular response to nitrogen compound. 20 possible pathways of HQHG in the treatment of ITP were identified through KEGG enrichment. EGFR, CASP3, TNF, and STAT3 are the four most important target proteins, while adenosine, caffeic acid, ferulic acid, quercetin-3β-D-glucoside, rutin, scopoletin, and tianshic acid are the most important active compounds, which were validated by molecular docking simulation. Conclusion. This study demonstrated that HQHG produced relief effects against ITP by regulating multitargets and multipathways with multicompounds. And the combined data provide novel insight of drug developing for ITP.