Abstract： Objective Exploring the mechanism of action of Radix Curcumae and Fructus Polygoni Orientalis on liver cancer based on network pharmacology prediction and cell experiment validation.Methods Screening the pharmacological active ingredients of Radix Curcumae and Fructus Polygoni Orientalis through TCMSP,organizing and correcting their corresponding target points of action.The liver cancer related gene targets through the Ctdbase database were searched.Using Venny to screen key targets for the treatment of liver cancer with Radix Curcumae and Fructus Polygoni Orientalis.Using STRING database for protein interaction(PPI)network analysis and GO and KEGG pathway enrichment analysis of key targets.Constructing a Component Target Disease Network Using Cytoscape.Detecting the effect of different concentrations of Radix Curcumae and Fructus Polygoni Orientalis extract on the survival rate of HepG2 cells.Using Western blot for detection of Akt,p-Akt,PI3K,and p-PI3K protein expression in HepG2 cells.Results Screening 28 active ingredients from Radix Curcumae and Fructus Polygoni Orientalis,with 547 targets for action and 35317 targets for liver cancer.45 core genes obtained through PPI network topology analysis.Key signaling pathways of Radix Curcumae and Fructus Polygoni Orientalis intervention in liver cancer identified through GO and KEGG enrichment analysis.In vitro experi-ments,it was showed that Radix Curcumae and Fructus Polygoni Orientalis has a significant inhibitory effect on HepG2 cell proliferation,downregulating the expression of Akt,p-Akt,PI3K,and p-PI3K proteins.Conclusion Radix Curcumae and Fructus Polygoni Orientalis has a significant inhibitory effect on liver cancer,and regulating the PI3K/Akt signaling pathway to inhibit liver cancer cell proliferation may be a partial mechanism of its action.