The choice of surgical modality for laparoscopic hepatectomy for hepatocellular carcinoma (HCC) has not been supported by high level of medical evidence hitherto. A prospective randomised controlled trial (RCT) was conducted to compare the perioperative and follow-up outcomes of patients with HCC treated by laparoscopic anatomical hepatectomy (LAH) and non-anatomical hepatectomy (LNAH).Between March 2013 and Jan 2018, eligible patients undergoing LAH and LNAH were enrolled and divided randomly into LAH group and LNAH group in this study. The perioperative and follow-up outcomes of both groups were compared and analysed.A total of 385 patients with HCC were randomly divided into LAH (n = 192) and LNAH (n = 193) groups. The groups were evenly matched for age, sex, liver background, segment involvement, tumor size, Child-Pugh grade and preoperative liver function. The operative time in the LAH group was longer than that of the LNAH group (p = 0.003). No significant between-group differences in intraoperative blood loss (p = 0.368), transfusion rate (p = 0.876), conversion to laparotomy rate (p = 0.365), overall complication rates (p = 0.054) were observed. The 1-year, 3-year and 5-year overall survival rates (OS) in the LAH group were 91.1%, 67.2%, 43.2%, respectively. The corresponding data in the LNAH group were 89.1%, 63.7%, and 35.2%, respectively. No significant difference was observed with regard to the 5-year OS rate (p = 0.054) between the two groups. The 1-year, 3-year and 5-year disease-free survival (DFS) rates in the LAH group were 87.0%, 54.7%, 33.9%, respectively. The corresponding data in LNAH group were 70.5%, 34.7%, and 30.1%, respectively. The 5-year DFS rate in the LAH group was significantly higher than that in the LNAH group (p = 0.009).LAH versus LNAH for selected HCC patients was associated with increased DFS, lower intrahepatic ipsilateral recurrence rate, comparable long-term OS and postoperative complications. LAH is therefore recommended for selected HCC patients.NCT02009176 (https://www.gov/).Copyright © 2022. Published by Elsevier Ltd.