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The Chinese herbal formula Tiao-Gan-Yi-Pi (TGYP) showed effective against Chronic Hepatitis B (CHB). In this study, we aimed to clarify the mechanisms and potential targets between TGYP and CHB through network pharmacology and molecular docking verification. The compounds of TGYP were identified in the TCMSP and CNKI databases, and their putative targets were predicted through SwissTargetPrediction and STITCH databases. The targets of CHB were obtained from the GeneCards, NCBI Gene, and DisGeNET databases. The above mentioned data were visualized using Cytoscape, and molecular docking showed the relationship between them. The expression of key targets was verified in GEO databases. Hence, we screened out 11 TGYP-related key targets for CHB included ABL1, CASP8, CCNA2, CCNB1, CDK4, CDKN1A, EP300, HIF1A, IGF1R, MAP2K1 and PGR. The key targets were predominantly enriched in the cancer, cell cycle and hepatitis B pathways and involved in the positive regulation of fibroblast proliferation, signal transduction, and negative regulation of gene expression biological processes, and expression of key target genes was related to HBV infection and liver inflammation. Through this newly constructed interaction network between TGYP and CHB, we identified active compounds and targets which could be further used for providing clinical guidance.