AIM: To evaluate the clinical utility of serum fibrosis markers,including YKL-40, in patients with HCV-associated liver disease.METHODS: A total of 109 patients with HCV-associated liver disease were enrolled. We measured serum type Ⅳ collagen, amino-terminal peptide of type Ⅲ procollagen (PⅢP),hyaluronic acid (HA), YKL-40 levels and biochemical.Parameters by RIA or ELISA. Eighty-eight patients underwent liver biopsy, and 67 of 109 patients received interferon (IFN)therapy. We also investigated the relationship between the concentrations of serum fibrosis markers and histological fibrosis scores (METAVIR), and evaluated the changes of the levels of fibrosis markers before and after the IFN therapy.RESULTS: The increase in serum levels of all markers,particularly HA, was correlated with the progression of liver fibrosis (for type Ⅳ collagen, F= 9.076, P＜0.0001; for PⅢP,F= 9.636, P＜0.0001; for HA, F= 13.128, P＜0.0001; and for YKL-40, F= 8.016, P＜0.0001). YKL-40 had strong correlation with HA (r= 0.536, P＜0.0001). Based on the receiver operating curve (ROC), the ability of serum HA exceeded the abilities of other serum markers to determine fibrosis score 4 from fibrosis score 0-3 (AUC = 0.854). While YKL-40 was superior to other fibrosis markers for predicting severe fibrosis (F2-F4) from mild fibrosis (F0-F1) (YKL-40, AUC = 0.809;HA, AUC = 0.805). After IFN therapy, only YKL-40 values significantly decreased not only in the responder group,but also in the nonresponder group (P = 0.03).CONCLUSION: YKL-40 may be a useful non-invasive serum marker to estimate the degree of liver fibrosis and to evaluate the efficacy of IFN therapies in patients with HCV-associated liver disease.