Background <p>RNA modifications play a pivotal role in regulating intracerebral hemorrhage (ICH). However, RNA modification-related genes (RMRGs) in ICH remain largely unexplored. This study aims to identify such biomarkers by integrating bulk and single-cell transcriptomic data.</p> Methods <p>Single-cell and transcriptomic data related to ICH were obtained from public databases, and RMRGs were sourced from existing literature. Differentially expressed genes were identified from the GSE216607 dataset and cross-referenced with RMRGs to generate candidate genes. Protein-protein interaction networks were then employed to identify core genes. Gene expression analysis of these core genes was conducted to pinpoint biomarkers in ICH. Functional enrichment analysis followed, and the expression of biomarkers in immune cells was examined. Additionally, drug predictions were made, and single-cell analysis was performed to characterize cell types and identify key cells based on biomarker expression.</p> Results <p>Ybx1 and Igf2bp2 were identified as biomarkers, with their expression levels upregulated in ICH samples from both the GSE216607 and GSE206971 datasets. Enrichment analysis indicated that these biomarkers are associated with neuronal systems and other related pathways. Further, these biomarkers were mapped to their human homologs, YBX1 and IGF2BP2. YBX1 exhibited the highest expression in non-classical monocytes, while IGF2BP2 was predominantly expressed in myeloid dendritic cells. Additionally, 3-butylidenephthalide, lithium chloride, and cantharidin were predicted as potential therapeutic agents for ICH. Single-cell analysis revealed monocytes and microglia 1 as key cell types.</p> Conclusion <p>Ybx1 and Igf2bp2 were identified as RM-related biomarkers in ICH, offering novel insights for ICH prevention and therapeutic strategies.</p>