Background: Atezolizumab-bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial, and is the new standard of care for first-line treatment of advanced HCC. However, the optimal sequence of therapy after failure of Ate/Bev is unknown. Regorafenib is an oral multikinase inhibitor that blocks the activity of protein kinases involved in angiogenesis, oncogenesis, metastasis, and tumour immunity. Although regorafenib showed survival benefit as subsequent treatment in patients with advanced HCC after progression on sorafenib, the efficacy and safety of regorafenib as subsequent therapy after Ate/Bev has not been investigated yet. Therefore, we designed a phase II trial investigating the efficacy and safety of regorafenib as second-line therapy in patients with advanced HCC who progressed on first-line Ate/Bev. Methods: This is a phase II, multicenter, single-arm study in patients with advanced HCC who had progression on first-line Ate/Bev. Additional key eligibility criteria include with Eastern Cooperative Oncology Group performance status 0–1, Child-Pugh score of 5 or 6, evaluable disease per RECIST v1.1, prior administration of at least 2 cycles of Ate/Bev, and adequate organ function. Key exclusion criteria include fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma, prior regorafenib treatment, clinically significant bleeding within 28 days of enrollment and untreated or symptomatic CNS or leptomeningeal metastasis. Eligible patients will receive oral regorafenib 160 mg daily for 3 weeks of every 4-week cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, time to progression, overall response rate (ORR), disease control rate and safety. ORR and PFS is assessed per RECIST v 1.1. This study is ongoing and 18 of planned 40 patients have been enrolled. This study is prospectively registered at ClinicalTrials.gov, NCT5134532.