Background and Aims Giant hepatic malignant tumor are generally poorly differentiated and often associated with vascular invasion. In recent years, the therapeutic efficacy for giant hepatic malignant tumor has been improved with the progress of both regional and comprehensive treatment. Surgical excision is one of the main treatment modalities. However, the operation is often difficult due to the intraoperative complexity such as tumor rupture, tumor thrombus spread, and omission of metastasis, which may cause the uncertainty of the treatment results. This study was performed to investigate the application and significance of intraoperative ultrasound (IOUS) and intraoperative contrast-enhanced ultrasound (CEIOUS) in the surgical treatment of giant hepatic malignant tumor, so as to help optimize the surgical procedure and obtain better oncological results.Methods The clinical data of 28 patients with giant hepatic malignant tumor undergoing surgical treatment under guidance of IOUS and CEIOUS at Hunan Provincial People's Hospital from January 2019 to August 2021 were retrospectively analyzed. All patients underwent laparotomy, and the pathological results, surgical methods, tumor size, tumor thrombus and intrahepatic metastasis, operative time, intraoperative bleeding and blood transfusion volume, postoperative hospital stay and postoperative complications were statistically analyzed.Results All patients underwent open surgery. The incisions included the inverse L-shaped incision (6 cases), fishhook-shaped incision (9 cases) and thoracicoabdominal incision (13 cases); all hepatic segments were involved in terms of the liver resection scope for the entire group, and some patients underwent combined resection of other organs; patients (11 cases) with visible vascular tumor thrombus underwent en-block resection of the primary tumor with the tumor thrombus (5 cases) or thrombectomy by venous incision (6 cases); the intrahepatic metastases (11 cases) identified by preoperative imaging examination and IOUS or CEIOUS were treated by excision or microwave ablation. The mean operation time was (365.18±110.45) min (range 190-560 min), the average blood loss was (598.21±414.43) mL (range 100-1 800 mL), 7 patients transfused with packed red cells during operation with an average infusion volume of (714.29±328.78) mL (range 400-1 300 mL), and 6 patients received fresh frozen plasma during operation with an average infusion volume of (325.00±117.26) mL (range 150-400 mL); the average number of hepatic inflow occlusion times was 4.82±2.36 (1-12 times). The postoperative pathological results showed that there were 24 cases of hepatocellular carcinoma, 2 cases of cholangiocarcinoma, 1 case of hepatocellular carcinoma with bile duct differentiation and 1 case of hepatoblastoma; the mean maximum diameter of the tumor was (13.07±3.57) cm (range 10-22 cm); there were 24 patients with microvascular tumor thrombus (including the 11 cases with visible vascular tumor thrombus). The mean hospital stay was (14.71±4.84) d (range 8-28 d). Clavien classification of surgical complications was grade I in 23 cases, grade II in 1 case and grade IIIa in 4 cases, respectively.Conclusion The application of IOUS and CEIOUS in the resection of giant hepatic malignant tumor can help optimize the surgical strategy and operation plan, identify the relationship between the tumor and blood vessels, and locate the tumor thrombus and metastatic lesions, which is of great significance to ensure the intraoperative safety, satisfactory postoperative recovery and long-term oncological outcomes.