GALAD is an algorithm model estimating the presence of hepatocellular carcinoma (HCC). However, the participants enrolled in the GALAD differ from those of Chinese subjects whose HCCs are mainly hepatitis B virus infection related. Therefore, the cross-sectional as well as longitudinal multicenter study was designed to assess the clinical performances of GALAD in the Chinese population.A case-control study of 602 patients with HCC (34.10% within Barcelona Clinic Liver Cancer 0-A stage) and 923 subjects without HCC from five Chinese medical centres was conducted. Longitudinally the performances of GALAD identifying HCC were assessed using receiver operating characteristic curves analyses. Furthermore, the surveillance performance of GALAD for 204 HCC patients after radical surgery and for the early detection of HCC prospectively in an independent cohort of chronic hepatitis B were analysed, respectively.We found the GALAD identified early stage HCC at an area under the receiver operating characteristic curve (AUC) above 0.85 and outperformed significantly than AFP, PIVKAII, AFP-L3 and BALAD-2 respectively. Meanwhile the GALAD could stratify HCC into two distinct subgroups with high or low risks of overall survival and recurrence. The GALAD could detection HCC 24 (AUC: 0.848) or even 48 (AUC: 0.833) weeks before clinical diagnosis.Our study indicates that the GALAD exhibits outstanding performance in the early diagnosis, prognosis prediction as well as risk monitoring of HCC in our cross-sectional and longitudinal multicenter study of 1561 patients. GALAD should be implanted into clinical practice early so as to improve the clinical efficacy of individual biomarkers in HCC early monitoring and prognosis prediction.© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.