BACKGROUND: The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. Percutaneous radiofrequency interstitial thermal ablation (RITA) has been shown to be efficacious in the treatment of unresectable HCC. Recent advances in laparoscopic ultrasound have greatly improved the accuracy in detecting intrahepatic HCC nodules, many of which were missed by computed tomography. Our objective was to introduce a novel operative combination of laparoscopic ultrasound with laparoscopic RITA in the treatment of HCC. METHODS: Eighty-eight patients with HCC in liver cirrhosis were submitted to laparoscopic RITA under sonographic guide. Most patients were in Child's A class of liver function. Patients with large tumors (> 5 cm), portal vein thrombosis, or severe liver disease (Child's C class) were excluded. RESULTS: The laparoscopic RITA procedure was completed in 86 of 88 patients (98% feasibility rate). Laparoscopy with laparoscopic ultrasound identified 23 new malignant lesions (27%) in comparison with the results of preoperative imaging. A total of 127 lesions were treated by RITA. There was no operative mortality. Sixty-one patients had no complication (71%). After a mean follow-up of 14.3 +/- 11.6 months, a complete response with a 100% necrosis was achieved in 70 of 83 patients examined (86%). During follow-up, 9 patients (11%) locally recurred at the RITA site and 38 patients (46%) had new malignant nodules. CONCLUSIONS: Laparoscopic RITA of HCC proved to be a safe and effective technique in the short term. This technique may be indicated when the percutaneous approach to the lesion is very difficult or if the patient is too ill to undergo laparotomy.