Aim To assess the safety and efficacy of percutaneous radiofrequency thermal ablation (RFA) in the treatment of nonsurgical hepatocellular carcinoma (HCC) in daily practice. Methods A total of 63 consecutive patients with HCC (solitary nodule <= 5cm or 2 nodules <= 3cm) and cirrhosis were treated with RFA. Majority of the patients had a compensated liver disease (73% Child A) and an early tumor stage (87% CLIP 0 or 1). Indications for treatment were primary HCC therapy (30 patients), adjuvant therapy before liver transplantation (115 patients) or palliation in the remaining 18 patients with progression of HCC despite previous antitumoral treatments. RFA was performed by a 100 kW electrical generator connected to an expandable 10-hook electrode. Results Seventy-one lesions were treated in 80 sessions. Sixteen patients required adjuvant chemoembolization. Mean follow-up was 18 12 months. An objective response was achieved in 87% of patients who underwent primary/adjuvant treatment. Complete histological necrosis was found in 38% of patients who underwent liver transplantation. One, 2 and 3-year survival rates were 95, 76 and 72%, respectively in patients who underwent primary/adjuvant therapy and 82, 68 and 51%, respectively in patients who underwent palliative therapy. Major complications (hemoperitoneum, pleuritis, pneumothorax and sepsis) were observed in 6.3% of the patients. Notably, rapid neoplastic progression was observed in two patients within 2 months after a single RFA session (neoplastic portal thrombosis and plurifocal HCC in one patient and cutaneous seeding and lung metastases in another patient). Conclusions Majority of the HCC patients treated by percutaneous RFA can achieve local control of the tumor in HCCs less than or equal to 3 cm. As the procedure can be associated with major complications and cases of rapid neoplastic dissemination may occur, a more accurate selection of candidates to RFA treatment is advisable.