Abstract: In December 1997, a prospective study with informed consent was initiated to test a neoadjuvant treatment of transcatheter hepatic arterial chemo-embolization (TACE) and thermal or chemical ablation followed by transcatheter hepatic arterial chemo-infusion (TACI) in patients with hepatocellular carcinoma (HCC) referred for transplantation (OLT) and for resection. Patients were staged with American Liver Tumor Study Group-modified tumour-node-metastasis (TNM) staging classification using serial 3–6 month physical exam, alphafetoprotein (AFP), abdominal enhanced MRI, chest CT and bone scan. Sixty-five patients with HCC, out of 508 patients referred for OLT, were divided into five clinical groups and an incidental HCC patient group (n = 8), diagnosed on post-transplant explant pathology. The key focus of study was safety, site of HCC recurrence and tumour free survival. One hundred and thirty three ablation, infusion procedures were performed with an overall 24.8% morbidity, including two septic deaths. There were 13 (21.6%) HCC recurrences in 60 patients having one or more ablative treatments with only 23% hepatic HCC recurrences at 43 months of study. Eighteen HCC patients were listed for OLT (Group 3), with 12 patients transplanted after 29–424 d waiting. Two patients were removed from the OLT list due to HCC metastases, waiting a mean of 145 d. Two patients, post-OLT, had their TNM score upgraded from T2, T3 to T4. No Group 3 post-OLT patient has died or had HCC recurrence at mean follow-up of 27 ± 15 months. No incidental HCC group post-OLT patient has died or had HCC recurrence at mean follow-up of 24 ± 14 months. This neoadjuvant protocol is safe and effective in reducing HCC recurrence prior to and after OLT and resection.