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Abstract: Only a small percentage of patients with large hepatocellular carcinoma (HCC) may benefit out of surgical resection. Thus, most of these patients are in need of a form of local control, such as ethanol ablation, transarterial chemoembolization (TACE), radiofrequency thermal ablation (RF), or laser induced thermotherapy (LITT). The purpose of this study was to assess the short-term effect of sequential RF and ethanol ablation in the management of large HCC (>5cm). Our series included 40 patients with large HCC tumors (>5cm in diameter). We adopted a protocol of overlapping RF applications, followed by repeated ethanol ablation sessions. Our results showed that the volume of tumor coagulative necrosis initially induced by RF has significantly risen after adjuvant ethanol ablation sessions (P < 0.001). Patients who achieved complete tumor necrosis after RF ablation were 52.5% of the series. This percent has jumped to 80% of the series at the end of the protocol. This indicates that such combined protocol is more effective than RF alone. Besides, it is valuable in reducing the number of RF sessions. [Copyright &y& Elsevier]