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AIM: To evaluate the detection and differentiation ability of contrast-enhanced intraoperative ultrasonography (CE-IOUS) in hepatocellular carcinoma (HCC) operations.METHODS: Clinical data of 50 HCC patients were retrospective analyzed. The sensitivity, specificity, false negative and false positive rates of contrast enhanced magnetic resonance imaging (CE-MRI), IOUS and CEIOUS were calculated and compared. Surgical strategy changes due to CE-IOUS were analyzed.RESULTS: Lesions detected by CE-MRI, IOUS and CEIOUS were 60, 97 and 85 respectively. The sensitivity,specificity, false negative rate, false positive rate of CEMRI were 98.2%, 98.6%, 98.6%, 60.0%, respectively;for IOUS were 50.0%, 90.9%, 1.8%, 1.4%, respectively;and for CE-IOUS were 1.4%, 40.0%, 50.0%,9.1%, respectively. The operation strategy of 9 (9/50,18.0%) cases was changed according to the results of CE-IOUS.CONCLUSION: Compared with CE-MRI, CE-IOUS performs better in detection and differentiation of small metastasis and regenerative nodules. It plays an important role in the decision-making of HCC operation.