Purpose: To investigate the Sonazoid-enhanced contrast-enhanced ultrasound (CEUS) features of hepatocellular carcinoma (HCC) in a non-cirrhosis liver background, in comparison to those in liver cirrhosis. Methods: In this retrospective study, 19 patients with surgery and histopathologically proven HCC lesions in non-cirrhosis liver background were included regarding Sonazoid-enhanced CEUS characteristics. Two radiologists evaluated the CEUS features of HCC lesions according to the WFUMB (World Federation of Societies for Ultrasound in Medicine and Biology) guidelines criteria. Thirty-six patients with HCC lesions in liver cirrhosis were included as a control group. Final diagnoses were confirmed by surgery and histopathological results. Results: Liver background of the non-cirrhosis group including normal liver (n = 7), liver fibrosis (n = 11), and alcoholic liver disease (n = 1). The mean size of non-cirrhosis HCC lesions was 60.8 ± 46.8 mm (ranging from 25 to 219 mm). During the arterial phase of Sonazoid-enhanced CEUS, most HCCs in non-cirrhotic liver (94.7%, 18/19) and in cirrhotic liver (83.3%, 30/36) presented non-rim hyperenhancement. During the portal venous phase, HCC lesions in the non-cirrhosis liver group showed relatively early washout (68.4%, 13/19) (p = 0.090). Meanwhile, HCC lesions in liver cirrhosis background showed isoenhancement (55.6%, 20/36). All lesions in the non-cirrhotic liver group showed hypoenhancement in the late phase and the Kupffer phase (100%, 19/19). Five cases of HCC lesions in liver cirrhosis showed isoenhancement during the late phase and hypoenhancement during the Kupffer phase (13.9%, 5/36). The rest of the cirrhotic HCC lesions showed hypoenhancement during the late phase and the Kupffer phase (86.1%, 31/36). Additional hypoenhanced lesions were detected in three patients in the non-cirrhosis liver group and eight patients in the liver cirrhosis group (mean size: 13.0 ± 5.6 mm), which were also suspected to be HCC lesions. Conclusions: Heterogeneous hyperenhancement during the arterial phase as well as relatively early washout are characteristic features of HCC in the non-cirrhotic liver on Sonazoid-enhanced CEUS.