Objective To explore the mechanism of Kuhuang injection in protecting the liver and alleviating jaundice by establishing the active components-target network and protein interaction network and analyzing the functions and pathways. Methods The main active components of Kuhuang injection were obtained through traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and related literatures. The targets to treat hepatitis and jaundice of the active components of Kuhuang injection were predicted and screened by GeneCard and online Mendelian inheritance in man (OMIM). Cytoscape 3.6.1 software was used to construct the active component-target network, and STRING database and Cytoscape 3.6.1 software were used to construct the protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways involved in the targets were analyzed using the database for annotation, visualization and integrated discovery (DAVID). Results The results showed that 16 active components of Kuhuang injection were screened and 85 targets were obtained. The results of network analysis showed that cellular processes, metabolic processes, and processes in response to stress were mainly involved in the effects of Kuhuang injection against hepatitis and jaundice. The results of target pathway analysis showed that the targets of Kuhuang injection for hepatitis and jaundice were mainly involved in mitogen-activated protein kinase (MAPK), Toll-like receptor, p53, neurotrophin and other signaling pathways. Conclusion The anti-hepatitis and jaundice effects of Kuhuang injection are characterized by multiple components, multiple targets and multiple pathways, which might be through regulating MAPK, Toll-like receptor, p53, neurotrophin and other related pathways.