Objective: To investigate the feasibility of “one-stop” surgical treatment for regional hepatolithiasis. Methods: The clinical data of 74 patients with regional hepatolithiasis admitted from January 2013 to August 2016 were retrospectively analyzed. All patients underwent “one-stop” surgical treatment, i.e., one-session performance of complete stone removal and resection of the biliary strictures and impaired portion of the liver based on regular liver resection and guided by intraoperative B-type ultrasonography and cholangioscopy. Results: In the 74 patients, the coincidence rate of stone distributions by preoperative imaging examinations was 94.6% (70/74). All patients underwent regular hepatectomy that included left hemihepatectomy in 21 cases, left lateral lobectomy in 8 cases, right hemihepatectomy in 17 cases, right posterior lobectomy in 16 cases, right anterior lobectomy in 4 cases, right posterior lobectomy plus left lateral lobectomy in 5 cases and extended right hemihepatectomy in 3 cases; anatomical hepatectomy was performed in 49 patients (66.2%); 5 of the 7 cases who had internal biliary-intestinal drainage previously underwent additional reconstruction of the anastomosis due to anastomotic stenosis; 71 cases underwent T-tube drainage, the other 3 cases did not undergo T-tube placement due to short length of the preserved common hepatic duct after reconstruction of the anastomosis; the average operative time was (235.7±35.6) min and the average of blood was (415.3±106.8) mL. No deaths occurred, and postoperative complications occurred in 11 patients, all of which were improved by conservative treatments; the average length of postoperative hospital stay was (9.2±4.1) d. Six patients with suspicious residual stones by postoperative T-tube cholangiography underwent outpatient cholangioscopy or stone extraction. All patients were followed-up for 3 to 24 months, biliary infection occurred once in the 2 cases who did not undergo reconstruction of the anastomosis of the previous biliary-intestinal drainage, and 21 patients had stone recurrence in the common bile duct and were treated by ERCP+EST. Conclusion: After rigorous preoperative evaluation and selection of suitable patients, “one-stop” surgical treatment for regional hepatolithiasis is safe and feasible, with favorable efficacy.