ObjectiveTo investigate the expression features of HBsAg and HBcAg in liver tissue and their correlation with HBV serum markers in children with chronic hepatitis B （CHB）. MethodsA total of 257 patients who were consecutively admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to December 2023 and underwent liver biopsy to achieve a confirmed diagnosis of CHB were enrolled in this study. The NIS-Elements system was used to capture the immunohistochemical images of HBsAg and HBcAg in liver tissues， and Image J software was used for quantitative analysis. The one-sample chi-square test was used for within-group comparison of continuous data， and the Pearson/Spearman/Kendall’s Tau-b correlation analysis was used to investigate the correlation between viral antigen expression and serological markers. ResultsAmong the 257 CHB patients， there were 162 children （76 children aged<5 years and 86 children aged 5 — 18 years） and 95 adults. There were significant differences in the expression pattern， area， and intensity of HBsAg and the area and intensity of HBcAg in liver tissue between different age groups and between the children with different HBeAg statuses （all P<0.05）. In the children aged<5 years， HBsAg staining area was significantly negatively correlated with anti-HBs and HBeAg （both P<0.05）and was significantly positively correlated with ALT and AST （both P<0.05）， and HBsAg staining intensity was significantly positively correlated with qHBsAg （P<0.05） and was significantly negatively correlated with anti-HBs （P<0.05）. In the children group， HBsAg staining area was negatively correlated with anti-HBs and HBeAg （both P<0.05）， and HBsAg staining intensity was positively correlated with qHBsAg （P<0.05） and was negatively correlated with anti-HBs （P<0.05）. In the adult group， HBsAg staining area was positively correlated with ALT， AST， and liver inflammatory activity （all P<0.05）， and HBsAg staining intensity was positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05） and was negatively correlated with liver inflammatory activity and fibrosis degree （both P<0.05）. In the children aged<5 years， HBcAg staining area was positively correlated with qHBsAg and HBV DNA （both P<0.05）， and HBcAg staining intensity was significantly positively correlated with HBV DNA （P<0.001）. In the children aged 5 — 18 years， the area and intensity of HBcAg staining were positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05）. In the children group， HBcAg staining area was positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05）， and HBcAg staining intensity was positively correlated with qHBsAg and HBV DNA （both P<0.05）. In the adult group， the area and intensity of HBcAg staining were positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.001）， and HBcAg staining area was positively correlated with the serum level of ALT （P=0.043）. ConclusionThe expression levels of HBsAg and HBcAg in liver tissue of children with CHB are significantly correlated with serological markers， and in clinical practice， HBsAg and HBcAg combined with serological markers can help to assess the condition of the liver， determine the immune stage， and provide evidence-based guidance for treatment timing.