Background and Aims Currently, Surgical resection is still the main radical approach for malignant liver tumors. However, sometimes due to reasons such as small tumor size, deep location, multiple occurrences, or secondary liver cancer forming "disappearing liver metastases" after drug treatment, it is challenging to accurately locate or detect the tumor during surgery. This study was performed to explore the application value of intraoperative contrast-enhanced ultrasound (CE-IOUS) in the surgery of malignant liver tumors.Methods A retrospective analysis was conducted on 56 patients with malignant liver tumors who were treated and underwent surgical resection at Zhongshan Hospital, Fudan University, from September 2022 to February 2023. The detection rates of liver lesions and the diagnostic accuracy rates for malignant tumors among preoperative enhanced magnetic resonance imaging (P-MRI), preoperative ultrasound (P-US), intraoperative ultrasound (IOUS), and CE-IOUS were compared.Results There were a total of 85 lesions in the 56 patients, among which, P-MRI detected 75 lesions, with postoperative pathology diagnosing 64 malignant lesions and 11 benign lesions, while 10 lesions were missed; P-US detected 46 lesions, with postoperative pathology diagnosing 30 malignant lesions and 16 benign lesions, while 39 lesions were missed; IOUS detected 64 lesions, with postoperative pathology diagnosing 44 malignant lesions and 20 benign lesions, while 21 lesions were missed; CE-IOUS diagnosed 78 lesions as malignant, with postoperative pathology confirming 66 malignant lesions and 12 benign lesions, while 7 lesions were missed. CE-IOUS had a significantly higher lesion detection rate compared to P-US and IOUS (91.8% vs. 54.1%, P<0.001; 91.8% vs. 75.3%, P<0.001) and a higher diagnostic accuracy rate compared to P-US and IOUS (86.8% vs. 65.2%, P<0.001; 86.8% vs. 68.7%, P<0.001). There was no statistically significant difference between CE-IOUS and P-MRI in terms of lesion detection rate, diagnostic accuracy for malignant tumors, and misdiagnosis rate.Conclusion Using Sonazoid contrast agent for CE-IOUS has a higher tumor detection rate and diagnostic accuracy for malignant liver tumors compared to P-US and IOUS. It can be used to identify and locate small lesions that cannot be displayed before surgery, to guide tumor resection or radiofrequency ablation and thereby improve surgical efficacy.