The purpose of this study is to evaluate high-intensity focused ultrasound (HIFU) ablation combined with transcatheter arterial chemoembolisation (TACE) in the treatment of larger hepatocellular carcinoma (HCC). Eighty-nine (89) patients with unrespectable larger HCC were randomised into a TACE group (n=45) and a TACE plus HIFU group (n=44). Therapeutic effects were assessed at follow-up with physical examination, level of serum alpha-fetoprotein and computed tomography or magnetic resonance imaging. All patients were followed up to observe long-term therapeutic effects and evaluated prognostic factors for survival. No severe complication was observed. Follow-up images showed that total effective rate in tumour response accounted for 72.8% in the TACE-HIFU group, which were significantly higher than that of TACE group (44.5%, P<0.05). The 1-, 2-, 3- and 5-year overall survival rates for the TACE-HIFU group were 72.7%, 50.0%, 31.8% and 11.4%, respectively; correspondingly, for the TACE group were 47.2%, 16.7%, 2.8% and 0%, respectively (P<0.01). The 1-, 2-, 3- and 5-year disease-free survival rates for the TACE-HIFU group were 34.1%, 18.2%, 9.1% and 0%, respectively; correspondingly, for the TACE group were 13.9%, 5.6%, 0% and 0%, respectively (P<0.01). TNM stage, portal vein tumour thrombosis and Child-Pugh classification each had a significant effect on the survival. HIFU ablation combined with TACE is safe, effective and a promising approach for the treatment of larger HCC.