The aims of this study were to evaluate the safety, feasibility and tumour response of _irreversible electroporation, a non-thermal ablation technique, for the treatment of unresectable hepatocellular carcinoma. The endpoints were safety and local treatment efficacy. Patients with unresectable tumours and tumours not amenable for radiofrequency _ablation because of their vicinity to organs vulnerable to thermal damage such as the bowel or because they were close to large blood vessels that would limit efficacy of ablation due to the heat sink effect were treated with irreversible electroporation using percutaneous _ultrasound and/or computed tomography guided electrode placement between November 2008 and _December 2009. Early, late, minor and major complications were recorded. Tumour response was determined on triphasic helical computed tomography follow-up at one month, then every three months post-procedure. Eleven patients received IRE therapy to 18 HCC lesions (Mean diameter 2.44 ± 0.99 cm; range 1.0-6.1 cm) with five patients having more than one treated HCC. Mean follow-up was 18 months (range 14-24 months). Six patients required repeat treatments for local residual or recurrent disease; two of these also had IRE for distant intrahepatic recurrence. No serious complications were observed despite seven lesions lying adjacent to important structures or organs. Four patients developed transient urinary retention and seven developed transient local post-procedure pain. After IRE therapy, 13 (72%) lesions were completely ablated with 93% success for lesions ≤ 3 cm (13/14). The local recurrence-free period was 18 ± 4 months and the distance recurrence free period was 14 ± 6 months. These preliminary results suggest that IRE is a safe and feasible technique for local ablation of HCC, particularly for lesions less than 3 cm. No major complications were encountered during this study even for tumours close to essential structures or organs.