Objective: To investigate the efficacy of liver resection based on pedicles of hepatic segments in treatment of hepatolithiasis. Methods: Using a prospective, cohort-controlled design, 90 patients with hepatolithiasis were randomly designated to study group and control group, with 45 cases in each group. Patients in study group underwent hepatectomy based on pedicles of hepatic segments and those in control group underwent hepatectomy based on Couinaud’s liver segment classification under ultrasound positioning. The main clinical variables between the two groups of patients were compared. Results: The general condition, liver function, stone distribution, bile duct variations and scope of liver resection showed no statistical difference between the two groups of patients before operation (all P>0.05). The intraoperative blood loss, incidence of postoperative complications, drainage volume and residual stone rate were significantly reduced in study group compared with control group (all P<0.05). The differences in operative time, blood transfusion rate, postoperative liver function, time to postoperative gas passage, and length of postoperative hospital stay showed no statistical significance (all P>0.05). Conclusion: Hepatectomy based on pedicles of hepatic segments has the advantages of small amount of blood loss and exudation as well as low rate of complications and residual stones, so it suitable to be used in treatment of hepatolithiasis.