The study compares immune cells in the liver of patients with HBV-induced cirrhosis and non-viral cirrhosis using single-cell RNA sequencing (scRNA-seq). They analyzed liver tissues from patients with HBV cirrhosis and healthy controls, integrating public single-cell and spatial transcriptomic data. In HBV cirrhosis, proinflammatory macrophage subsets-PLCG2 and CD8+ T-FABP5 were found to be expanded, while macrophages-CD5L, CD4+ T-ANXA1, CD4+ T-CCR6 and CD4+ T-CER were decreased. Macrophages-PLCG2 was associated with Rap1 signaling, macrophages-CD5L with lysosomal pathways. Spatial analysis showed colocalization of myeloid T cells in HBV cirrhosis. Enhanced HLA-E/KLRK1 signaling between myeloid and NK cells was identified in HBV cases (p < 0.05). The study highlights the heterogeneity of immune cells and potential therapeutic targets such as macrophage-PLCG2 and CD8+ T-FABP5. The findings point to the role of immune dysregulation in the progression of HBV cirrhosis.