LAUSR

&NA; In our previous studies, vitamin C (VC) exerts potent pharmacological activities against liver injury (LI). Therefore, this report was designed to use network pharmacology‐based strategy to predict therapeutic targets of VC against LI, and further to investigate the pharmacological molecular mechanisms. Pathological targets of LI were identified, followed by acquisition of verified targets of VC. After constructing target‐functional protein interaction network of VC against LI, the core therapeutic targets of VC against LI were obtained. Further, biological function and pathway enrichment analyses were performed on core therapeutic targets to evaluate the biological processes and key signaling pathways of VC against LI. As revealed in network pharmacology assays, 6 key therapeutic targets for VC against LI were identified, showing tumor necrosis factor (TNF), nuclear factor‐kappa‐B p65 (RELA), nuclear factor‐kappa‐B p105 (NFKB1), TNF receptor‐associated factor 2 (TRAF2), interleukin 6 (IL‐6) and interleukin 1 beta (IL1B). On the basis of data analyses from DAVID database and omicshare cloud platform, bio‐functional enrichment assays showed that the therapeutic effects of VC against LI were closely associated with regulating inflammatory reaction and apoptosis. Further, pathway enrichment analysis indicated the anti‐LI benefits of VC were principally implicated in regulating the top 20 signaling pathways, such as inflammation‐associated TNF signaling pathway, NF‐&kgr;B signaling pathway. Taken together, the bioinformatics data elucidate that anti‐LI pharmacological activities of VC may be predominantly related to inhibition of inflammatory stress, contributing to suppression of LI development. These resultant findings highlight the predicted therapeutic targets may be potential biomarkers for anti‐LI. HighlightsPathological targets of LI are identified before mapping.Biological targets of VC are verified before mapping.Top 6 key therapeutic targets of VC‐exerted anti‐LI are identified.VC against LI is closely linked to regulating development of inflammation.Predicted targets of VC may be potential biomarkers for anti‐LI.