EgyptAim: This study aimed to assess the diagnostic value of serum cytokeratin-18 in children with chronic liver diseases (CLD) and correlate its serum level with liver histology and other liver biomarkers. Methods: This study included two groups, the first group included children with CLD and the second group included healthy matched age and gender subjects as a control group, complete history and clinical examination, and serum CK-18 was measured using the sandwich enzyme-linked immunosorbent assay technique. Results: Serum concentrations of CK-18 were significantly elevated in CLD patients with mean AE standard deviation (1070.63 AE 699.2 ng/mL) compared to healthy controls mean AE standard deviation (203.95 AE 83.57 ng/mL). CK-18 levels were associated with a change in hepatocyte and portal tract (P = 0.005) as it was elevated with cirrhosis and fibrosis stage (P = 0.02) as it was elevated with moderate and severe fibrosis than mild fibrosis, also it showed a gradual increase in accordance with child Pugh score. There was a positive correlation between CK-18 levels and Total IgG, paediatric end-stage liver disease score and model for end-stage liver disease scores, the best cutoff point of CK-18 was 624 ng/mL, with sensitivity 93.06%, specificity 62.5% and diagnostic accuracy 90.0% for detection of fibrosis. Conclusion: CK-18 could be used as a non-invasive diagnostic marker in children with CLD.