Chronic infection with the hepatitis B virus (HBV) is a significant contributor to severe liver diseases, including cirrhosis and hepatocellular carcinoma, thereby posing a substantial global health concern. This investigation employed an HBV transgenic mouse model harboring mutations in the basal core promoter (BCP) region to assess the model’s virological characteristics and hepatic damage. The extent of liver fibrosis was determined using sirius red staining of liver tissue. Furthermore, whole-genome transcriptomic analysis of liver tissue was conducted. The study revealed that 12-week-old HBV transgenic mice with BCP region mutations exhibited increased HBV DNA replication levels and spontaneous liver fibrosis. Differential gene expression analysis identified 729 upregulated and 325 down-regulated genes within the HBV-Tg cohort, which predominantly associated with the extracellular matrix, peroxisome proliferator-activated receptor (PPAR) pathway, and cytochrome P450 pathway. Protein-protein interaction (PPI) network analysis indicated that pivotal genes were implicated in collagen synthesis, inflammatory response, cell cycle regulation, and apoptosis. The pathological alterations observed in this murine model align with the progression of chronic liver disease, thus providing a robust and effective model for elucidating the mechanisms underlying HBV infection-related hepatic pathology.