Objective:The aim of this study is to discover the possible working mechanisms of Ardisiae Japonicae Herba(AJH)on hepatoma carcinoma(HCC).Methods:In this study,ethanol extract of AJH was prepared and used to treat HCC cell in vitro.Furthermore,a genomic wide RNA sequencing(RNA-seq)was performed to screen deregulated genes in HCC cells after the treatment of AJH extract.The gene and protein expression related to lipid metabo-lism in HCC cells were also investigated to validate the results obtained from RNA-seq.Results:AJH extract could inhibit HCC cell proliferation in vitro.RNA-seq analysis has identified 1,601 dif-ferentially expressed genes(DEGs,fold change≥2.0 or fold change≤0.5,P<0.05)in HCC after AJH extract treatment,which included 225 up-regulated genes and 1,376 down-regulated genes.KEGG path-way analysis of DEGs demonstrated that lipid metabolism was a potential pathway related to AJH treat-ment.In agreement with the RNA-seq data,qPCR and Western-blot analysis indicated that expression of genes and proteins related to lipid metabolism(SREBP1,ACC,ACLY and FASN)were significantly down-regulated in AJH treatment group as compared with the control group.Furthermore,AJH extract could also decrease lipid contents and cellular free fatty acid levels in HCC cells.Conclusion:Ethanol extract of AJH could inhibit HCC cell proliferation in vitro,the possible mechanism may be related to the inhibition of lipid metabolism.