Objective: This study was conducted to explore the potential association between berberine and multiple organ dysfunction syndrome (MODS) induced lung disease by pharmacological analysis. Methods: By using the keywords “MODS”, “lung disease”, and “berberine” to search related targets in the GeneCards database, protein-coding options, Venn graph, and String database were combined to construct a protein interaction network and screen core targets. Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID database, followed by analysis and construction of the disease-site-drug-key target-KEGG pathway network via Cytoscape software. Results: 33 cross genes were identified by the Venn graph tool, but only 32 have connections. 10 Core targets were identified in protein interaction networks, which are IL6, IL1B, TNF, TLR4, INS, CASP3, HIF1A, PTGS2, NFKB1, and STAT3. GO and KEGG analyses revealed that those core targets were enriched in positive regulation of interleukin-8 production, extracellular space, identical protein binding, etc. Finally, the disease-site-drug-key target-KEGG pathway network was constructed to decipher the association among MODS, lung, and berberine. Conclusions: The results provide clues to understand the potential mechanism of action of berberine in MODS-induced lung disease, and therefore provide valuable information for subsequent network mechanism explanation.