Aim: Non-invasive assessment of changes in liver fibrosis is still an unmet medical need in the era of antiviral therapy. Therefore, we explore whether chitinase 3-like 1 (CHI3L1), a serum marker of liver fibrosis, can be used as a non-invasive surrogate marker of fibrosis change during treatment. Methods: We correlated serum CHI3L1 levels with liver tissue collagen proportionate area (CPA) in a cohort of 131 patients with chronic hepatitis B (CHB) receiving entecavir-based antiviral therapy for 78 weeks. In addition, we compared this marker with the liver stiffness measurement (LSM). Multivariate regression analyses were undertaken to determine the clinical factors associated with the CHI3L1 levels. Results: Before treatment, correlation analysis showed that there were positive correlations between CHI3L1 levels and the CPA (r = 0.351, P < 0.001), and between CHI3L1 and LSM (r = 0.412, P < 0.001). After 78 weeks treatment, serum CHI3L1 levels decreased compared with that at baseline (87.8 vs. 69.6 ng/mL, P < 0.001), and CHI3L1 levels were also correlated with CPA (r = 0.293, P = 0.001) and LSM (r = 0.443, P < 0.001). Furthermore, there were positive correlations between the changes in CHI3L1 and CPA (r = 0.366, P < 0.001), and changes in CHI3L1 and LSM (r = 0.438, P < 0.001). Multivariate regression analyses indicated that CPA values were related with pre- (beta = 5.450, P = 0.019) and post-treatment CHI3L1 levels (beta = 7.460, P = 0.023). Conclusions: Chitinase 3-like 1 is not only a useful noninvasive marker for the assessment of liver fibrosis in CHB patients before treatment, but also a potential useful marker for monitoring the change in liver fibrosis during therapy.