Objective Exploring the relationship between changes in serum Golgi apparatus transmembrane glycoprotein 73 （GP73） and chitosanase 3-like protein 1 （CHI3L1） levels and liver fibrosis and lesion severity in patients with hepatitis B （CHB）. Methods Using a case-control study， 80 patients diagnosed with CHB infection and developing liver fibrosis in the Infectious Disease Department of Changsha First Hospital from June 2020 to June 2023 were selected as the liver fibrosis group， while 120 patients diagnosed with CHB infection but not developing liver fibrosis in the Infectious Disease Department of our hospital were selected as the control group. The serum GP3， CHI3L1， liver function， and fibrosis indicators of the two groups of patients were compared， and the liver fibrosis group was divided into mild according to Scheuer system standards Perform stratified analysis on patients with significant liver fibrosis. Results The serum GP3 and CHI3L1 levels in the liver fibrosis group were significantly higher than those in the control group， with statistical significance （P < 0.05）； The ROC curves were plotted using serum GP3， CHI3L1， and GP3 + CHI3L1， respectively. The sensitivity for diagnosing liver fibrosis in CHB patients was 62.81%， 60.94%， and 96.33%， with specificity of 80.66%， 80.05%， and 75.30%. The AUC values under the curves were 0.792， 0.756， and 0.908， respectively； The levels of ALT， AST， HA， LN， PC III NP， C IV， and CG in the liver fibrosis group were higher than those in the control group， and the PLT measurement values were lower than those in the control group， with statistical significance （P < 0.05）； 49 patients with moderate to severe liver fibrosis （33 in S2 phase and 16 in S3 phase） and 31 patients with mild liver fibrosis （all in S1 phase） had significantly higher serum GP3 and CHI3L1 levels than mild patients， with statistical significance （P < 0.05）； The levels of DBIL， ALT， AST， HA， LN， PC III NP， C IV， and CG in patients with moderate to severe liver fibrosis were higher than those in the mild group， and the PLT measurement values were lower than those in the mild group， with statistical significance （P < 0.05）. Conclusion The serum GP3 and CHI3L1 levels in CHB patients with liver fibrosis are significantly elevated， and there is a certain correlation with the degree of liver fibrosis. The combination of these two indicators is beneficial for diagnosing liver fibrosis in CHB patients.