Background. There are still controversies about the curative effect of vitamin C in treating HIE, and its mechanism of action is not entirely clear. This study is designed to explore the potential molecular mechanism of vitamin C in treating neonatal hypoxic ischemic encephalopathy (HIE). Methods. The effect targets of vitamin C and the pathogenic targets of neonatal HIE were obtained via retrieval of public databases to screen out the molecular targets of vitamin C acting on neonatal HIE. Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the main targets. Vitamin C and the optimum target structural components are subjected to molecular docking and molecular dynamics simulation analysis via computer software so as to verify their binding activity and stability. Result. Based on 16 overlapping targets of vitamin C and HIE, seven main targets were identified in this study. According to GO and KEGG analysis, molecular functions (top 25 items) and signal pathways (21 items) related to inflammatory reaction, immune response, and cell transcriptional control may be potential pathways for vitamin C to treat neonatal HIE. Molecular docking and molecular dynamics simulation were adopted to definitively determine the 4 optimum core target spots. Conclusion. The efficacy of vitamin C on HIE is involved in the immunoregulation and inflammation-related functional processes and signal pathways. These molecular mechanisms, including core targets, will contribute to the clinical practice of neonatal HIE in the future.