ObjectiveTo investigate the clinical diagnostic value of extra-spindle pole-like protein 1 （ESPL1） in the progression of hepatitis B virus （HBV）-related liver fibrosis. MethodsA total of 228 patients with HBV infection who were admitted to The First Affiliated Hospital of Guangxi Medical University from June 2017 to August 2023 were enrolled. The transient elastography system FibroScan was used to determine liver stiffness measurement （LSM） for all patients， and according to the LSM value， they were divided into non-liver fibrosis group with 80 patients， mild liver fibrosis group with 83 patients， advanced liver fibrosis group with 30 patients， and liver cirrhosis group with 35 patients. ELISA was used to measure the serum level of ESPL1. The Kruskal-Wallis H test was used for comparison of the serum level of ESPL1 between the four groups； the Spearman correlation analysis was used to investigate the correlation between ESPL1 and LSM； the receiver operating characteristic （ROC） curve was used to analyze the value of serum ESPL1 in predicting the progression of liver fibrosis. ResultsThe liver cirrhosis group had a significantly higher serum level of ESPL1 than the non-liver fibrosis group and the mild liver fibrosis group （both P<0.05）， and the advanced liver fibrosis group and the mild liver fibrosis group had a significantly higher serum level of ESPL1 than the non-liver fibrosis group （both P<0.05）. The correlation analysis showed that there was a positive correlation between serum ESPL1 and LSM in the patients with HBV infection and varying degrees of liver fibrosis （r=0.515， P<0.001）. Serum ESPL1 had an area under the ROC curve （AUC） of 0.809 in predicting liver cirrhosis and an AUC of 0.638 in predicting advanced liver fibrosis， with a sensitivity of 87.5% and 100%， respectively， and a specificity of 59.7% and 31.3%， respectively. ConclusionThere is a certain correlation between serum ESPL1 and HBV-related liver fibrosis， and higher serum ESPL1 may indicate a higher degree of liver fibrosis. Serum ESPL1 is expected to become one of the serum markers for assisting in the diagnosis of liver cirrhosis and an important clinical method for dynamically monitoring the progression of liver fibrosis in patients with HBV infection.