Objective:To investigate the safety and outcomes of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in hepatocellular carcinoma (HCC).Methods:The clinical data of HCC patients who underwent hepatectomy at the University of Hongkong-Shenzhen Hospital from April 2014 to December 2020 were retrospectively analyzed. Of 57 HCC patients who were enrolled, there were 43 males and 14 females, aged (51±14) years old. According to the surgical method, the patients were divided into two groups: patients with pre-operative residual liver volume/standard liver volume <30% who underwent ALPPS procedure by anterior approach formed the study group ( n=20), and patients who underwent right hepatectomy with residual liver volume/standard liver volume ≥35% formed the control group ( n=37). Clinicopathological data and prognosis were reviewed and compared between the two groups. The patients were followed up via outpatient service and telephone. Results:There were more patients with well-moderately differentiated HCC in the study group than in the control group, and the difference was statistically significant ( P<0.05). All patients in the study group successfully completed two-step hepatectomy. Compared with the control group, the operative duration [644(535, 780) vs. 352 (269, 401) min], intraoperative blood loss [1 650 (1 338, 2 200) vs. 650 (500, 925) ml], and proportion of patients requiring blood transfusion (60.0% vs. 29.7%) were increased in the study group. The difference was statistically significant ( P<0.05). There was no significant difference in the incidence of grade III or higher complications between the study group and the control group [30.0% (6/20) vs. 18.9% (7/37), χ 2=0.91, P=0.341]. The 1-, 2- and 3-year overall survival rates were 90.0%, 63.8% and 46.4% respectively, and the corresponding tumor-free survival rates were 53.3%, 35.6%, and 35.6% respectively for the study group. The 1-, 2-, and 3-year overall survival rates were 71.4%, 63.4%, 51.7%, and tumor-free survival rates were 39.0%, 18.5%, 9.3% in the control group respectively. There was no significant difference in the postoperative survival rate and tumor-free survival rate between the two groups ( P>0.05). Conclusion:ALPPS was safe and feasible for treatment of right hepatocellular carcinoma with insufficient residual liver volume, and its survival outcomes was similar with one-stage right hepatectomy for HCC patients.