Aims: Sorafenib is the only standard therapy for advanced hepatocellular carcinoma, but has a low response rate. Leucovorin and oxaliplatin (FOLFOX) has a superior response rate versus doxorubicin among Asian sorafenib-naive patients. We aimed to retrospectively review the outcome of 20 consecutive patients treated with FOLFOX at a single European center. Materials & methods: Patients had symptomatic disease burdens unlikely to regress with sorafenib or had no proven treatment options (sorafenib-refractory or recurrence post liver transplantation). Results: One sorafenib-refractory patient had a complete response and two liver transplant patients experienced partial responses. Median overall survival was 6.3 months. There was one chemotherapy death due to neutropenic sepsis. Conclusion: In advanced hepatocellular carcinoma, FOLFOX can induce clinically relevant responses, but needs prospective validation.