Objective:To predict the mechanism of Radix Paeoniae Rubra in the treatment of hepatocellular carcinoma(HCC)by network pharmacology.Methods:Through TCMSP database(https://tcmspw.com/tcmspsearch.php)，the chemical constituents of Radix Paeoniae Rubra were searched，and the targets of Radix Paeoniae Rubra were predicted by STD database and SEA database. Through OMIM database(http://www.omim.org)，drugbank database(https:// www.drugbank.ca/)and TTD database(http://db.idrblab.net/ttd/)，the corresponding targets of HCC were collected. Then, the common targets from both active ingredient targets and HCC disease targets were obtained. The String platform was used to collect liver cancer disease-related target proteins, and GO analysis was performed with David database. Protein-protein interaction (PPI) network was constructed by Cytoscape 3.2.1 software, and the core targets were obtained by topological analysis. The mechanism of Radix Paeoniae Rubra on HCC was further analyzed.Results:A total of 28 compounds and 442 targets from Radix Paeoniae Rubra were obtained from TCMSP database. A total of 148 HCC-related disease targets were retrieved from OMIM, DrugBank and TTD databases. Twenty-three common targets from both active ingredient targets and HCC disease targets were obtained. There were 193 nodes and 722 edges in the protein- protein interaction network，and 95 nodes，439 edges and 21 core targets were obtained by topological index screening. A total of 561 biological processes，85 cellular components and 130 molecular functions were obtained by GO annotation.Conclusion:Network pharmacology intuitively shows that Radix Paeoniae Rubra has multiple components，multiple targets and multiple pathways in the treatment of HCC. This study provides a theoretical basis for the follow-up development of medicines for the treatment of HCC.