BACKGROUND: Glypican-3 (GPC-3) is a key regulator of a variety of physiological processes, including cellular growth, differentiation, and cell proliferation, and morphogenesis, particularly in hepatocytes. This study aimed to assess serum GPC-3 levels in children with biliary atresia (BA) and its correlation with clinical parameters. METHODS: In this case-control study 50 children, with biliary atresia, and 50 healthy children as controls. All children were diagnosed with biliary atresia based on clinical, laboratory, and histological findings of liver biopsy. All children had their medical histories were taken, complete clinical examination, and serum GPC3 levels by ELISA. RESULTS: Glypican 3 was statistically higher in the biliary atresia group (7.26 ± 3.48 ng/ml) than the control group (1.7 ± 0.52 ng/ml), p < 0.001. Also, it was higher in BA with jaundice (9.1 ± 2.66 ng/ml) than BA without jaundice (3.6 ± 1.2 ng/ml) and controls, p < 0.001. Moreover, GPC-3 was higher in BA patients with portal hypertension (PH) (9.35 ± 2.3 ng/ml), than patients without PH (5.78 ± 1.9 ng/ml), and controls p < 0.001. There was a statistically significant positive correlation between serum level of GPC-3 and liver stiffness by fibroScan, ALT, AST, Total bilirubin, direct bilirubin, while there was a statistically significant negative correlation between serum level of GPC-3 and platelets, total protein, and serum Albumin. CONCLUSION: In biliary atresia, serum GPC-3 is a valuable noninvasive marker for detecting deterioration of hepatic function and the degree of liver fibrosis.