Background and Aims Hepatolithiasis is one of the most common digestive system diseases, which can progress to liver cirrhosis, biliary tract infection, liver abscess, and even cholangiocarcinoma. Hepatectomy remains the thorough treatment method for hepatolithiasis. In recent years, with the advancement of technology, laparoscopic surgery has gradually replaced open surgery due to its superiority in short-term therapy effects. However, compared to hepatobiliary tumors, the inflammation, edema, and adhesion caused by hepatobiliary stones make the surgery more difficult. Therefore, it is necessary to find a simple and reliable surgical approach. Recently, with a renewed understanding of liver anatomy, laparoscopic extra-Glissonean anatomic hepatectomy has become widely used in liver tumors, and there have been reports confirming that its combination with indocyanine green (ICG) fluorescence negative staining technique can enhance the efficiency and precision of surgery. However, its application in hepatolithiasis has been rarely reported. Here, the authors summarize and compile their recent experiences applying the extra-Glissonean approach combined with ICG fluorescence-negative staining in treating hepatolithiasis.Methods The clinical data of seven patients with hepatolithiasis treated in the Department of Biliary Surgery of Xiangya Hospital, Central South University, from February 2022 to April 2023, were retrospectively analyzed. Based on the medical history, clinical symptoms, and preoperative imaging data, all patients exhibited indications for liver resection. Six patients underwent left hepatectomy, and one underwent right posterior lobectomy. Intraoperatively, fluorescence laparoscopy was employed. Under low central venous pressure and total hepatic inflow occlusion, anatomical landmarks on the liver surface (including the Arantius plate, cystic plate, umbilical plate, and Glissonean pedicle of the caudate process) and the Laennec's capsule were utilized to dissect the target hepatic pedicle anatomically. After occlusion, ICG was injected into the peripheral veins, resulting in ischemia/resection demarcation lines on the liver surface. Then, an anatomic hepatectomy was completed with intraoperative exposure of the hepatic vein. In some patients, bile duct incision and intraoperative cholangioscopy were additionally performed to enhance stone clearance rates.Results All seven patients successfully underwent liver resection surgery, and postoperative specimens were dissected to examine and confirm the status of the removed stones. Five patients underwent choledocholithotomy and intraoperative choledochoscopy after liver resection. Intraoperative blood loss ranged from 100 to 600 mL, with an average of (314.3±211.6) mL. No severe complications (Clavien-Dindo grade Ⅲ-Ⅳ) occurred. Except for one patient who was hospitalized for 24 d due to postoperative bile leakage and wound infection, the length of postoperative hospital stay in the remaining patients ranged from 7 to 9 d, with an average of (8.5±0.8) d. Postoperative abdominal ultrasonography, T-tube cholangiography, or MRCP examination revealed complete stone clearance in 6 patients, and in 1 patient, the stones were completely removed after an additional postoperative choledochoscopic lithotomy. Pathological examination results for all cases indicated hepatolithiasis and cholangitis, with no evidence of canceration.Conclusion The application of laparoscopic extra-Glissonean anatomic hepatectomy combined with ICG fluorescence-negative staining in patients with hepatolithiasis is safe and feasible. Its effectiveness and superiority still require further validation through controlled studies with expanded sample sizes and enriched clinical data.