Objective To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis. Methods In vivo experiments were conducted using a rat model of carbon tetrachloride ( CCL4 )-induced liver cirrhosis. Rats were divided into normal, model, colchicine,JWJSSQ low-dose, JWJSSQ medium-dose, and JWJSSQ high-dose group. Pathological changes in liver tissues in each group were examined by hematoxylin and eosin( HE) and Masson staining, changes in serum liver function were detected using test kits, levels of hyaluronic acid (HA), laminin (LN), procollagen Ⅲ (PCⅢ), and collagen type Ⅳ (COL4) were detected by enzyme-linked immunosorbent assay(ELISA), and protein expression levels of hypoxiainducible factor-1α (HIF-1α), Notch1, Jagged1, and α-smooth muscle actin (α-SMA) were detected by Western blot. In vitro experiments were conducted in HSC-T6 cells, and the optimal concentration of CoCl₂(100 μmol / L, 200μmol / L, 400 μmol / L, 600 μmol / L and 800 μmol / L) in the cultured cells and the optimal concentration of drugcontaining serum (5%, 10%, 15%, 20%) were determined by Cell Counting Kit-8(CCK-8) assay. The migration ability of cells in each group was detected by scratch testing, and changes in the apoptosis rates were determined by flow cytometry. Protein expression levels of HIF-1α, Notch1, Jagged1, α-SMA, matrix metallopeptidase 9 (MMP9), and tissue inhibitor of metalloproteinases 1 (TIMP-1) were detected by Western blot. Results In the in vivo experiments, liver swelling, inflammatory cell infiltration, collagen deposition, and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group. Serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), HA, LN, PCⅢ, and COL4 were significantly increased and albumin(ALB) was significantly decreased in the model group, while liver levels of HIF-1α, Notch1,Jagged1, and α-SMA proteins were significantly increased (P<0. 01). Liver swelling, inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced. Serum ALT, AST, HA, LN, PCIII, and COL4 were significantly decreased and ALB was significantly increased, while liver levels of HIF-1α, Notch1, Jagged1, and α-SMA proteins were also significantly decreased to varying degrees ( P<0. 05). In the in vitro experiments, hypoxia promoted HSC-T6 migration and reduced apoptosis, increased the protein expression levels of HIF-1α, Notch1, Jagged1, α-SMA, and TIMP-1, and reduced the expression levels of MMP9 (P<0. 01). Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration, promoted HSC-T6 apoptosis, lowered the expression of HIF-1α, Notch1, Jagged1, α-SMA, and TIMP-1 proteins, and enhanced the expression of MMP9 protein (P<0. 01). The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine. Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/ Notch pathway, thereby exerting an anti-liver cirrhosis effect.