Ultrasound (US)-guided ethanol injection therapy is becoming popular as a therapeutic tool for treating hepatocellular carcinoma (HCC); however, there are some HCCs seen on computed tomography (CT) and not visualized on US. The aim of this study was to learn whether ethanol could be injected into such tumors correctly using a specially designed needle-guide for intercostal puncture on US. We developed a new needle-guide attachment for US. In vitro experiments were done with gelatin gel and porcine liver to evaluate the accuracy of the puncture depth. We calculated the difference between the distance from the surface to the needle tip and the set depth as errors. Fifteen patients with HCC in which CT revealed a tumor but US did not were subjected to US-guided ethanol injection using this needle-guide, and the entry of ethanol into tumors was confirmed by subsequent enhanced CT. The errors were within 1.0 mm in the in vitro experiments using gelatin gel and porcine liver. In all HCC patients, ethanol was injected accurately. This new needle-guide may be useful for needle insertion to HCCs seen on CT and not visualized on US.