Objective Transcriptome sequencing technology (RNA-seq) was used to analyze the mechanism of compound Dancao granules in the intervention of high-fat feed combined with carbon tetrachloride (CCl4) induced non-alcoholic steatohepatitis. Methods 45 male C57BL/6 mice were split into two groups at random: normal control group,model control group, obeccholic acid group (10mg/kg/d), Compound Dancao Granules low and high dose groups (10.71g/kg/d, 21.42g/kg/d), with 9 mice in each group. Normal diet was served to the control group, and the mice in the model group were given high-fat diet combined with subcutaneous injection of CC14, 100%CC14 solution (4mL/kg) for the first time, and 40% CC14-olive oil solution (2mL/kg) for the second time, twice a week for a total of 6 weeks. Each drug group was administered from week 3 for a total of 4 weeks. 12h after the last administration, serum and liver tissues of mice in each group were collected and biochemical kit was used to detect serum liver function. Hematoxylin-eosin (HE), Sirius scarlet, and oil red O stainings were used to examine the histopathological changes of the liver. Differential genes were analyzed by RNA-seq and performed functional enrichment analysis, in order to verify the expression of differential gene mRNA, the quantitative real-time polymerase chain reaction was used, and TDT-media atedDuTPnick-endlabeling (TUNEL) staining was used to identify the apoptosis. Results Model control groups had significantly higher levels of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), and triglycerides(TG) than normal controls. (P < 0.01). Additionally, There was obvious inflammatory cell infiltration in liver tissue, collagen deposition in sink area and interlobule, and significant increase in lipid droplet area (P<0.01)..The levels of TC, TG, ALT, and AST were significantly lower in the groups receiving compound Dancao granules and obeccholic acid than in the model control group. (P < 0.01), inflammatory cell infiltration, collagen deposition and fat accumulation in the sink area and interlobule were improved (P<0.01). RNA-seq sequencing results showed that 2819 genes in the normal control group were differentially expressed compared with the model control group, 543 up-regulated genes and 2276 down-regulated genes. Between the model control group and the compound Dancao granules group, 240 genes were differentially expressed, including 206 up-regulated genes and 34 down-regulated genes. There were 221 overlapping genes in the two groups, and the functional enrichment mainly focused on cell cycle(CDT1, PLK1, BUB1B, TTK, KNL1, ESCO2, CDC6, NDC80, CDC25B, SGO1, CCNB2, ESPL1, CCNE1, MCM4, MCM5, FBXO5, BUB1, MCM2), apoptosis（Caspase-3，Bax，P53，Apaf1，Bak，Caspase-8）, P53 signaling pathway（P53, CCNB2, APAF1, BAK, BAX, GTSE1, CASPASE-3, CCNE1）, arachidonic acid metabolism（HPGDS, CYP2C54, CYP2B10, TBXAS1, CYP2C50）, galactose metabolism（HK3, GLA, HK2, AKR1B7） and other signaling pathways. RNA-seq sequencing analysis showed that compound Danicao granules mainly regulated apoptosis signaling pathway, and quantitative PCR confirmed that compared with normal control group, mRNA expressions of Caspase-3，Bax，P53，Apaf1，Bak and Caspase-8 in liver tissue of model control group were increased (P < 0.01). Compared with model control group, mRNA expressions of Caspase-3，Bax，P53，Apaf1，Bak and Caspase-8 in liver tissue of compound Dancao granules group were decreased (P < 0.01). TUNEL staining showed that the number of cell nuclear shrinkage and apoptotic bodies decreased in the group of compound Dancao granule administration. Conclusion Compound Dancao Granule has a significant protective effect on non-alcoholic steatohepatitis induced by high fat feed combined with CCl4, and its mechanism might be connected to the control of genes linked to apoptosis.