OBJECTIVE: To investigate the relationship between tissue inhibitor of metalloproteinase-1 (TIMP-1) expression and the severity of liver fibrosis in chronic hepatitis B (CHB) patients, and to explore the diagnostic value of serum TIMP-1. METHODS: A total of 159 CHB patients underwent liver biopsy for the analysis of liver fibrosis stages and inflammation. Serum TIMP-1 was determined by ELISA. Hyaluronic acid (HA), procollagen type III (PCIII), collagen type IV (CIV), laminin (LN), and FIB-4 index were determined and calculated, and diagnostic accuracy was analyzed using receiver operating characteristic (ROC) curve. RESULTS: Serum levels of TIMP-1 were associated with the grade of liver inflammation in CHB patients (r = 0.695, P < 0.01), especially in those without fibrosis or with stage 1 fibrosis, and were also positively correlated with liver fibrosis in CHB patients (r = 0.854, P < 0.01), particularly in those with inflammation at grade 1, 2 and 3. The area under the ROC curve (AUROC) of serum TIMP-1 was 0.918 for significant liver fibrosis (>= stage 2), and a sensitivity of 89.4% and specificity of 83.6% were obtained with a cut-off value of >= 174.5 ng/mL of serum TIMP-1, which were higher than that of HA, CIV and FIB-4 index. CONCLUSION: TIMP-1 is a valuable single biomarker for the evaluation of significant fibrosis in CHB patients.