Hepatic epithelioid angiomyolipoma (EAML) has malignant potential that can easily be misdiagnosed as hepatocellular carcinoma (HCC), but the treatment options of these conditions are different. This retrospective study investigated whether contrast-enhanced ultrasound (CEUS) can differentiate EAML from HCC. We included 24 patients with pathologically confirmed EAML and 36 patients with HCC who underwent pre-operative conventional ultrasound and CEUS. The conventional ultrasound and CEUS features of the two groups were analyzed. Time intensity curves (TICs) were analyzed for all lesions using quantitative perfusion analysis software. This study found that significant differences existed between the EAML and HCC groups in terms of clinical features such as sex, age, symptoms, alpha-fetoprotein and history of hepatitis B virus infection (p < 0.05). Tumor size, number, border and echogenicity on conventional ultrasound were significantly different between EAML and HCC (p < 0.05). Regarding CEUS, EAML was more likely to have a centripetal enhancement pattern than HCC (p < 0.05). The tumor enhancement degree in the delayed phase in CEUS was significantly different between EAML and HCC (p < 0.05). Quantitative analysis of CEUS parameters revealed that the wash-in area under the curve (AUC) was larger in EAML than in HCC (p < 0.05). Time to peak was significantly shorter in EAML than in HCC (p < 0.05). The peak intensity was significantly stronger in EAML than in HCC (p < 0.05). Regarding the diagnostic performance of CEUS parameters that showed statistical significance on univariate analysis, the sensitivity and specificity for distinguishing EAML from HCC was 66.7%-100.0% and 55.6%-91.7%, respectively. Overall, CEUS could be valuable in differentiating EAML from HCC. Specific features such as the centripetal filling and prolonged enhancement patterns on CEUS, higher peak intensity, bigger wash-in AUC and shorter time to peak on TICs may contribute to a more confirmative differential diagnosis of EAML. (E-mail: Liky20006@126.com) (C) 2020 World Federation for Ultrasound in Medicine & Biology. All rights reserved.