Worldwide, hepatocellular carcinoma (HCC) occurs mainly in Asian patients with hepatitis B virus (HBV) infection. This study aimed to decipher the environmental and virological factors associated with HCC occurrence and validate risk scoring systems in a French multicenter prospective cohort of HBV-cirrhotic patients. Patients with biopsy-proven Child-Pugh A viral cirrhosis included in the ANRS CO12 CirVir cohort who were HBsAg(+) without hepatitis C co-infection were selected for: i) interview through a standardized questionnaire reporting coffee consumption and HCC familial history; ii) HBsAg quantification using baseline and sequential two-year frozen sera; iii) baseline HBV genotype determination; and iv) assessment of risk factors and applicability of HCC risk scores (Kaplan-Meier analysis, Cox models). Among 317 patients studied (261 men, median age 53 years, past or ongoing antiviral treatment 93.3%, and baseline detectable HBV DNA in 88 patients), the baseline and 2-year median HBsAg levels were 810 and 463 IU/mL, respectively. After a median follow-up of 65.2 months, 27 HCC cases were diagnosed (annual incidence: 1.6%). Three factors were independently associated with HCC occurrence: age >50 years, platelets ≤150 x 10 /mm and body mass index ≥30 kg/m . Two out of five risk scores were validated, and the most accurate was PAGE-B at one year. Moreover, HCC in patients without maintained virological suppression seem more aggressive and less accessible to curative treatment. In CONCLUSION: in French patients with HBV cirrhosis mostly virally suppressed, independent HCC risk factors were host-related (age, obesity) or linked to the severity of cirrhosis (thrombopenia), and the European PAGE-B score was the most accurate risk score. This article is protected by copyright. All rights reserved.