The combination of high-intensity focused ultrasound (HIFU) and transarterial chemoembolization (TACE) has been experimentally performed in a variety of malignant tumors, and its validity has not yet been evaluated for hepatoblastoma (HB). We evaluated the disease-response rate, resection rate, and toxicity in children with unresectable or metastatic HB (stage III and stage IV HB) after sequential treatment with TACE plus HIFU in a controlled clinical trial. The 35 patients with unresectable or metastatic HB were nonrandomly assigned to HIFU ablation (n = 12) or C5V chemotherapy (n = 23). The rates of complete resection, tumor response, and treatment toxicity were evaluated for both regimens. Nine patients who received C5V and 10 patients who received TACE plus HIFU became operable (P = .02). The 3-year event-free survival and overall survival rates were 43.03% and 56.68% in the C5V group and 38.57% and 57.86% in the TACE plus HIFU group, respectively. Acute grade 3 or 4 adverse events, including neutropenia, thrombocytopenia, and anemia, were more frequent in patients treated with C5V therapy than in patients receiving TACE plus HIFU. HIFU ablation achieved a higher rate of complete resection and a lower rate of severe complications compared with C5V treatment in children with advanced HB (Chinese Clinical Trials Registry No. ChiCTR-PRCH-08000182).