Objective To evaluate the clinical value of the American College Radiology Liver Imaging Report and Data System（LI-RADS）classification criteria with contrast- enhanced ultrasound in the diagnosis and differential diagnosis of hepatocellular carcinoma（HCC）.Methods From January 2018 to December 2019, A total of 163 patients (192 lesions) with focal liver lesion who had high risk of HCC and were diagnosed in the First Affiliated Hospital of Jinzhou Medical University were selected. Retrospective analysis of the contrast-enhanced ultrasound images of all patients was performed, and all lesions were classified according to ACR CEUS LI-RADS standard, using histopathological diagnosis as the gold standard. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of CEUS LR-RADS classification criteria in the diagnosis of hepatocellular carcinoma were calculated. The ROC curve was constructed and the area under the curve was calculated.Results A total of 192 nodules was found in 163 patients, including 145 case of HCC (75.5%), 10 case of ICC (5.2%), 4 case of HCC-ICC (2.1%), 2 case of metastatic tumors (1.0%), and 31 case of benign lesions (16.1%), and all lesions were confirmed by pathology. The CEUS LI-RADS classification results showed: 17 cases were LR-3 classification (8.9%), 33 cases were LR-4 classification (17.2%), 120 cases were LR-5 classification (62.5%), and 22 cases were LR-M classification (11.5%). The PPV of HCC in each category were 17.6% (3/17), 51.5% (17/33), 98.3% (118/120), and 31.8% (7/22), respectively. The sensitivity, specificity and PPV of LR-5 in the diagnosis of HCC were 81.4%, 95.7%, and 98.3%, respectively. With the combination of LR-4 and LR-5, the sensitivity, specificity, and PPV were 93.1%, 61.7% and 88.2%, respectively; the AUC were 0.886 (95% CI: 0.836, 0.937) and 0.782 (95% CI: 0.696, 0.868), with statistically significant differences (P < 0.05). In LR-M, 95.5% (21/22) of the lesions were malignant, of which 31.8% (7/22) were HCC and 63.6% (14/22) were non-HCC malignant lesions. All HCC are correctly classified as LR-M. Most (75%) of LR-3 were benign lesions.Conclusions American College Radiology contrast-enhanced ultrasound LI-RADS has high application value in the diagnosis and differential diagnosis of HCC, and excellent risk prediction value for patients with high risk of HCC. It can be recommended for clinical practice.