AIM: To investigate the long-term outcome and prognostic factors when treating hepatocellular carcinoma (HCC) with thermal ablation. MATERIALS AND METHODS: A total of 846 HCC patients, diagnosed histopathologically and/or radiologically, underwent thermal ablation from October 2001 to May 2013. Thermal ablation included both radiofrequency ablation (RFA) and microwave ablation (MWA), and was performed by percutaneous, open, and laparoscopic approaches. Clinical data, especially focused on disease-free survival, were retrospectively analysed by univariate and multivariate analyses. RESULTS: A total of 1,185 thermal ablation treatments were performed, corresponding to 1,240 tumours. The complete ablation rate was 97.1%. The 12-, 24-, 36-, and 60-month disease-free survival rates after thermal ablation were 72.3%, 52.7%, 33.5%, and 16.1%, respectively. Multivariate analysis indicated that the serum alkaline phosphatase levels (ALP) and the number of tumours were independent risk factors affecting disease-free survival. The 12-, 36-, 60-, 84-, and 120-month overall survival rates of all patients were 92.9%, 74.7%, 58.1%, 41.3%, and 15.8%, respectively. Multivariate analysis indicated that age, ALP, number of tumours, and treatment sessions per case were independent risk factors related to overall survival. CONCLUSIONS: Thermal ablation was a relatively safe and effective procedure. Patients with increased serum ALP levels and/or multiple tumours had a higher incidence of recurrence and poorer prognosis, and therefore, should be monitored closely in clinical practice. (C) 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.