Current literature on the role of contrast-enhanced ultrasound (CEUS) in the diagnosis of hepatocellular carcinoma (HCC) in non-cirrhotic patients is limited. The aim of this retrospective multicenter study was to analyze CEUS features of histologically proven HCC in patients with non-cirrhotic liver. In this multicenter study, 96 patients from eight medical institutions with histologically proven HCC lesions in non-cirrhotic liver were retrospectively reviewed regarding SonoVue-enhanced CEUS features. Two ultrasound experts assessed the CEUS enhancement pattern and came to a consensus using the World Federation of Societies for Ultrasound in Medicine and Biology guideline criteria. The mean size of HCC lesions included was 60.3 ± 37.8 mm (mean ± standard deviation). Most of the lesions were heterogeneous but predominantly hypo-echoic on B-mode ultrasound (64.5%, 62/96), with ill-defined margins and irregular shapes. During the arterial phase of CEUS, most of the HCC lesions in non-cirrhotic liver exhibited heterogeneous hyperenhancement (78.1%, 75/96) compared with the surrounding liver parenchyma. Almost 30% of HCC lesions (28.1%, 27/96) exhibited early wash-out (<60 s). All lesions exhibited wash-out and hypo-enhancement in the late phase. CEUS features of HCC lesions in non-cirrhotic patients typically include hyperenhancement in the arterial phase and relatively rapid wash-out in the portal venous phase, which is different from HCC in cirrhotic livers and more similar to liver metastasis.