BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a prevalent and deadly disease with limited treatment options. Regorafenib, a tyrosine kinase inhibitor, has shown promise in HCC treatment but faces limitations as a monotherapy. Combining regorafenib with PD-1 inhibitor may improve efficacy and survival outcomes for patients. This retrospective analysis was conducted to explore its efficacy and safety, providing reference experience for better application of this combination therapy. METHODS: This retrospective single-center study evaluated the efficacy and safety of combining regorafenib with PD-1 blockade for patients with HCC. Efficacy was evaluated according to the RECIST 1.1 evaluation criteria. Safety was assessed using CTCAE 4.0. Data was analyzed to compare survival status in different subgroups. RESULTS: Generally, there were 76 patients with HCC elected to receive the regorafenib plus PD-1 blockade treatment during the study period. The objective response rate was 21.1% ( = 16), and the disease control rate was 56.6% ( = 43). Median progression-free survival (PFS) was 6.8 months, and median overall survival had not yet been reached. All patients suffered of at least 1 adverse event. Grade ≥3 adverse events occurred in 31.6% of patients ( = 24), with the most common being hand-foot syndrome, decreased appetite, and abdominal distension. Subgroup analyses showed no significant differences in PFS based on cirrhosis status or previous treatment lines. CONCLUSION: With manageable safety, regorafenib combined PD-1 inhibitor could bring survival benefits for advanced HCC who have received systemic treatment. Further, the Cox analysis showed that HBV infection, metastasis, etc. did not have significant effects on the survival benefits.