Objective Gancao（Licorice）,a traditional Chinese herbal drug,has been extensively applied to treat diseases in clinical. However,the pharmacological mechanisms of Gancao in treatment of Hepatocellular carcinoma（HCC）still remain equivocal. In this study,a network pharmacology?based methodology was used to elucidate its underlying mode of action. Methods We gathered candidate compounds and potential targets of Gancao based on TCMSP and potential targets of HCC relied on Gene? Cards and OMIM databases,and a Disease?Compound?Target network was built. Furthermore,A total of 93 effective compounds and 89 putative targets of Gancao were selected and GO and KEGG enrichment analysis were applied to investigate the molecular mechanism. Results The results indicated that potential targets of Gancao treating HCC are mostly involved in diversified pathways associated with Cancer ?related pathway,HBV pathway,HCV pathway,Apoptosis pathway,TNF pathway and MAPK pathway.Importantly,PPARG,AR,ESR2 and GSK3B exhibited higher interactive with other proteins and RAF1 participated in 8 signaling pathways related with liver diseases. EGFR and CCND1 took part in 6 cancer?related pathways while MYC and RB1 were active in 3 liver?related pathways. Conclusion In all,Gancao could attenuate HCC via regulating multiple molecules and pathways associated with proliferation,apop?tosis and inflammatory response.