〔Abstract〕 To investigate the effect of HQJND on acute liver injury in severely scalded rats and its possible molecular mechanism by animal experiments and modern pharmacological tools. Methods Firstly, the rat model of sepsis was established and randomly divided into 4 groups. The normal saline group was given 1 mL of normal saline twice a day, and the traditional Chinese medicine group was given 1 mL of concentrated Huangqi Jiuni decoction twice a day. After 72 hours of shock, the samples were sacrificed, and then the serum liver function and (+)-haematoxylin eosin staining were performed to verify the efficacy of the drug. Sham Operation Group and sepsis group were fed normally without any special treatment. Then, network pharmacology was used to screen the targets of drugs and drug responses and predict the signaling pathways that might play a role in the treatment of diseases. Finally, fluorescence quantitative PCR (RT-qPCR) was performed to detect gene expression, Western blot (WB) was performed to detect Tumor necrosis factor (TNFα), P65, phosphorylated P65 (P-P65), and immunohistochemical (IHC) were performed assays to verify drug efficacy and explore the mechanism of drug treatment. Results Serum liver function and histopathology in rats showed that HQJND significantly improved liver function in severely burned rats. Network pharmacology screening was used to identify 353 disease-related marker genes and 286 drug targets. It was predicted that tumor necrosis/NF-NF-κB pathway (TNF/NF-NF-κB pathway) might be a key pathway for HQJND to treat acute liver injury after severe burns. The results of immunohistochemistry (IHC) showed that the staining of TNF-α in the liver of the sepsis group was more than that of the Sham Operation Group and the traditional Chinese medicine group. The results of fluorescence quantitative PCR (RT-qPCR) and Western blot (WB) showed that the expression of TNF-α, TNFR1 and P65 proteins in the liver of rats in the sepsis group was significantly higher than that in the Sham Operation Group and the traditional Chinese medicine group; on the contrary, the expression of TNF-α, TNFR1 and P65 proteins in the liver of rats in the sepsis group was significantly higher than that in the Sham Operation Group and the traditional Chinese medicine group. The expression level of IKBα was higher in the Sham Operation Group and the traditional Chinese medicine group, indicating that drug treatment effectively inhibited the activation of the TNF/NF-κb signaling pathway and alleviated the inflammatory response, thereby alleviating tissue damage. Conclusion Animal experiments and network pharmacology results confirm that HQJND has a protective effect on acute liver injury in severely burned rats, which may be related to the inhibition of TNF/NF-κB signaling pathway.