Chronic hepatitis B (CHB) is a global public health concern characterized by multiple disease stages. Existing CHB research is largely constrained by limited access to infection sites, with most studies relying on peripheral samples such as blood, which inadequately elucidate the interplay among liver parenchyma, the immune microenvironment, and viral dynamics. Only a few studies have employed multi-omics technologies to analyze liver biopsy tissues, revealing molecular differences at the hepatic level. This study represents the first large-scale proteomic analysis of different clinical stages of CHB in liver tissue.