Background: Non-invasive biomarkers have largely replaced liver biopsy in assessment of liver fibrosis in chronic HCV. Autotaxin (ATX) is a novel serum marker that may be related to liver fibrosis. Aim: to clarify the role of ATX as a biomarker for the estimation of hepatic fibrosis and to compare its sensitivity and specificity to the well-known fibrosis-4 score (FIB-4) and the AST-to-Platelet Ratio Index (APRI) before treatment with direct-acting antiviral drugs (DAAs) for chronic HCV as well as six months after the end of treatment. Methods: Plasma samples were obtained from 86 chronic HCV patients with different degrees of liver fibrosis. Routine laboratory, transient elastography (TE) and ultrasonographic assessments were done. Enzyme-linked immunosorbent assay (ELISA) technique was used to detect ATX. Results: ATX, FIB-4, and APRI had AUC of 0.57, 0.95, and 0.92, respectively for the detection of cirrhosis (F4). Baseline ATX was higher in cirrhotic group vs. non-cirrhotic group (250 vs. 210) pg/ml, although the difference was not significant (p= 0.3). Significant improvement of all the laboratory parameters, APRI, FIB-4 and liver stiffness occurred at sustained virological response after 24 weeks (SVR24). Non- significant increase of ATX level was noted six months after the end of treatment. Conclusion: ATX should be considered cautiously as a diagnostic marker for liver fibrosis in patients with chronic HCV.