BACKGROUND/AIM: This study aimed to assess the clinical impact of lenvatinib after disease progression on atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 14 patients who received lenvatinib after failure of atezolizumab plus bevacizumab and all patients were classified as having a Barcelona Clinic Liver Cancer stage C. Six patients had macrovascular invasion, and a liver occupation rate of >50% was reported in seven patients. The Kaplan-Meier method was performed to analyze the cumulative survival, while log-rank test was used to detect the differences. The dose of lenvatinib was determined based on body weight. RESULTS: The participants' responses to lenvatinib treatment were as follows: 21.4% achieved partial response (PR), while 35.7% had a stable disease, with a disease control rate of 57.1%. The median progression-free survival (PFS) and overall survival (OS) were 4.2 months and 8.3 months, respectively; the median PFS and OS were 6.7 months and 10.5 months in the PR group. No significant difference was observed in the median PFS and OS between patients with and without macrovascular invasion or liver occupation rate of >50%. Most of the adverse events (AEs) were categorized as grade 1-2; all patients tolerated the AEs, and no drug-related mortality was reported. Additionally, half of the population underwent subsequent therapy after progression on lenvatinib treatment. CONCLUSION: Lenvatinib is effective and can be safely used as second-line systemic therapy after progression on atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice.