BackgroundAtezolizumab-bevacizumab (atezo-bev) is recommended as first-line therapy for patients with unresectable hepatocellular carcinoma (uHCC). However, its effectiveness and safety in other populations, including those with Child-Turcotte-Pugh (CTP) class B cirrhosis, is unclear. MethodsFor this systematic review and meta-analysis, electronic databases, including PubMed, Embase, and Scopus, were searched from 1st May, 2020 till 5th October, 2022; the last date of access was January 31, 2023. Pooled progression-free survival (PFS), overall survival (OS), and radiological response rate among patients receiving atezo-bev were compared between patients with CTP-A and CTP-B cirrhosis, with tyrosine kinase inhibitors (TKIs) and among those receiving the drug as first-line and later line therapy. The protocol was registered in Prospero (CRD42022364430). FindingsAmong 47 studies (n = 5400 patients), pooled PFS and OS were 6.86 (95% CI, 6.31-7.41) and 13.8 months (95% CI, 11.81-15.8), respectively. Objective response rate (ORR) and disease control rate were 26.7% (24.6-29.1) and 75.3% (73.1-77.4) using RECIST criteria, and 34% (30.3-37.8) and 73.6% (68.8-78) using mRECIST criteria, respectively. Among those receiving atezo-bev, patients with CTP-B cirrhosis had similar ORRs by RECIST (odds ratio OR, 1.42 0.77-2.6; P = 0.25) and mRECIST criteria (OR, 1.33 0.52-3.39; P = 0.53) but shorter PFS (mean difference MD:3.83 months 1.81-5.84) than those with CTP-A cirrhosis. Compared to patients receiving TKIs, those receiving atezo-bev had longer PFS (MD: 2.27 months 0.94-3.5) and higher ORR (RECIST: OR, 1.44 1.01-2.04 and mRECIST: OR, 1.33 1.01-1.75). Compared to first-line therapy, later-line therapy had lower ORR (RECIST: OR, 1.82 1.3-2.53; P < 0.001 and mRECIST: OR, 2.02 1.34-3.05) but comparable PFS (MD: 0.58 months -0.18 to 1.35) among nine studies. The incidence of grade ≥3 adverse events among patients with CTP-A and CTP-B cirrhosis was comparable (OR, 0.89 0.45-1.74) as it was for patients receiving atezo-bev and TKIs (OR, 0.86 0.61-1.2). InterpretationOur findings suggest that atezo-bev is safe and effective as first-line systemic therapy for patients with uHCC and CTP-A or CTP-B cirrhosis. FundingAn unsolicited grant from ROCHE Products India Pvt Ltd. was received for publication.