Background: The GALAD score is a serum biomarker–sensitivity of 91% and a specificity of 85% for HCC detection. based model that predicts the probability of having The AUC of the GALAD score for early-stage HCC detection hepatocellular carcinoma (HCC) in patients with chronic remained high at 0.92 (95% CI, 0.88–0.96; cutoff 1.18, liver disease. We aimed to assess the performance of the sensitivity 92%, specificity 79%). The AUC of the GALAD GALAD score in comparison with liver ultrasound for score for HCC detection was 0.88 (95% CI, 0.85–0.91) in the detection of HCC. EDRN cohort. The combination of GALAD and ultrasound Methods: A single-center cohort of 111 HCC patients and (GALADUS score) further improved the performance of the 180 controls with cirrhosis or chronic hepatitis B and a GALAD score in the single-center cohort, achieving an AUC multicenter cohort of 233 early HCC and 412 cirrhosis of 0.98 (95% CI, 0.96–0.99; cutoff 0.18, sensitivity 95%, patients from the Early Detection Research Network (EDRN) specificity 91%). phase II HCC Study were analyzed. Conclusions: The performance of the GALAD score was Results: The area under the ROC curve (AUC) of the GALAD superior to ultrasound for HCC detection. The GALADUS score for HCC detection was 0.95 [95% confidence interval score further enhanced the performance of the GALAD score. (CI), 0.93–97], which was higher than the AUC of ultrasound Impact: The GALAD score was validated in the United (0.82, P <0.01). At a cutoff of 0.76, the GALAD score had a States.