The purpose of this preclinical study was to use an in vivo tumor-mimic model on pig liver for evaluating the accuracy of large HIFU ablations as required for human treatments. Tumor-mimics were created in in vivo porcine livers by injecting a 1 cc warm mixture of agarose, cellulose, glycerol and methylene blue, which formed 1 cm hyperechoic discrete lesions on sonograms. Three studies were conducted: (i) in vitro experiments were carried out to study the acoustical proprieties of the tumor-mimics, (ii) in vivo experiments were conducted in 10 pigs to evaluate the tolerance of the tumor-mimics and the evolution of their dimensions at mid-term (30 days), (iii) in vivo ultrasound-guided HIFU ablations have been performed in 10 pigs to demonstrate the feasibility of treating accurately a predetermined zone. Thereby, elementary lesions at 10 mm from the tumor-mimic were created. In addition, HIFU ablations were performed by juxtaposing single lesions to surround tumor-mimics with an average margin of 2 mm in all directions. It has been shown that the acoustical properties of tumor-mimics made them visible on sonograms and did not modify the shape and dimensions of HIFU lesions. The local and biological tolerances of tumor-mimics were excellent. Tumor-mimics were measured on sonogram with reproducible dimensions (average diameter at DO: 9.7 plusmn 1.0 mm (range 5.6-12.0 mm)), similar to those measured on the sample removed after surgery (average diameter at DO: 10.1 plusmn 0.7 mm (range 6.3-11.5 mm)). HIFU ablations at 10 mm from the tumor-mimics were measured on the sample at 11.3 plusmn 1.0 mm (range 8.0-14.0 mm), this is a 13% difference. In addition, it has been showed that 90% of the margins established with juxtaposed HIFU ablations were upper than 2 mm. Therefore this tumor-mimic can be used to learn HIFU ablation before starting clinical studies especially when the ultrasound device is to be used manually as the one presented in this study.