Histone methylation, a critical epigenetic modification, is meticulously regulated by specific methyltransferases and demethylases. Changes in the methylation levels at specific histone sites play a key role in gene transcription regulation, inflammatory responses, and disease progression. Alternations in the levels of histone methylation and the expression of associated modifying enzymes contribute significantly to the pathogenesis of chronic liver diseases, including viral hepatitis, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. This review summarizes recent research advances regarding histone methylation and inhibitors of associated modifying enzymes in the context of chronic liver diseases, aiming to provide a reference for the translational application of basic research into clinical therapies for these conditions.