Background: Intermediate-stage hepatocellular carcinoma (HCC) is a heterogeneous disease; therefore, the efficacy of transarterial chemoembolization (TACE) is affected by tumor burden, resulting in a wide range of survival outcomes. Multiple recent guidelines suggest that systemic therapy is preferable for patients with intermediate-stage HCC who are TACE unsuitable because of high tumor burden, such as beyond up-to-seven criteria. The Phase III IMbrave150 study established atezolizumab plus bevacizumab (atezo+bev) as the standard of care in patients with unresectable HCC. Here, we investigated whether atezo+bev is potentially superior to TACE in efficacy and safety in TACE-naïve patients with unresectable intermediate-stage HCC beyond up-to-seven criteria. Methods: In this multicenter, phase II study, atezo 1200 mg + bev 15 mg/kg q3w were administered to eligible patients (as defined above plus having Child-Pugh A liver function) enrolled from Dec 2020 to Sep 2021 until discontinuation due to disease progression, adverse events (AEs), or other reasons. Overall survival (OS) follow-up continued for 2.5 years after enrolment. The primary endpoint was progression-free survival (PFS) assessed by mRECIST by investigator; secondary endpoints were objective response rate (ORR), PFS by RECIST v1.1, OS, and safety. In an exploratory analysis, we conducted propensity score matching (PSM) analysis to compare the efficacy between atezo+bev and TACE, the data of which were retrospectively collected in patients treated with TACE in each participating center from Jan 2017 to Dec 2017. Results: In total, 74 patients were enrolled (male, 87.8%; mean age, 73.7 years; median [range］maximum tumor diameter by pre-treatment CT, 4.8［1.0,13.0］cm). Median (min, max) follow-up was 15.0 (1.6, 21.6) months. Median PFS was 9.1 (95%CI: 7.1, 10.2) months (by mRECIST; primary endpoint). ORR was 45.9 (95%CI: 34.3, 57.9) % by mRECIST. Median OS was not reached (NR) (95%CI: NR, NR). 12-month OS rate was 84.6 [95%CI: 74.0, 91.2]%. The most frequent AEs (any grade ≥10% of patients) were hypertension, proteinuria, malaise, anorexia, edema, pruritis, and diarrhea. Conclusions: Atezo+bev provides clinical benefits to TACE-unsuitable patients with intermediate-stage HCC beyond up-to-seven criteria. Results of the exploratory PSM analysis will be presented. Clinical trial information: jrcts071200051.