Objective: To determine the efficacy of anatomic segmental hepatic resection under real-time ultrasound navigation in treatment of hepatocellular carcinoma (HCC). Methods: The clinical data of 30 HCC patients undergoing anatomic segmental hepatic resection under real-time ultrasound navigation (observation group) and 30 HCC patients who were subjected to non-anatomic liver resection (control group) from June 2014 to June 2015 in Anhui Provincial Hospital of Anhui Medical University were reviewed. The main clinical variables between the two groups of patients were compared. Results: The preoperative data between the two groups of patients were comparable. In observation group versus control group, the operative time was prolonged (153.5 min vs. 128.5 min, P<0.05), and the intraoperative blood loss showed no significant difference (175.0 mL vs. 200.00 mL, P>0.05), but the intraoperative blood transfusion rate (10.0% vs. 36.7%, P<0.05) and hepatic portal occlusion rate (16.7% vs. 40.0%, P<0.05) were significantly reduced. There was no significant difference in incidence of postoperative complications between the two groups (13.3% vs. 33.3%, P>0.05). In observation group, the 1-year recurrence rate was significantly lower than that in control group (16.7% vs. 43.3%, P<0.05), while 1-year survival rate was significantly higher than that in control group (80.0% vs. 53.3%, P<0.05). Conclusion: Application of anatomic segmental hepatic resection under real-time ultrasound navigation has a beneficial effect on reducing postoperative recurrence and improving prognosis in HCC patients.