Background and Aims Currently, the indications for laparoscopic hepatectomy in the treatment of hepatocellular carcinoma (HCC) have gradually converged with those for open hepatectomy, and the feasibility, safety, and effectiveness of laparoscopic hepatectomy have been progressively confirmed. However, surgeons often exhibit selection bias in choosing the surgical method. Therefore, the choice between laparoscopic and open hepatectomy also needs careful evaluation in different patient populations and medical centers. Despite this, doubts still persist among scholars regarding the oncological outcomes of laparoscopic hepatectomy. Therefore, this study was conducted to analyze and compare the clinical efficacy of laparoscopic versus open hepatectomy in the treatment of HCC.Methods The clinical data of 517 patients who underwent hepatectomy for HCC in Xiangya Hospital, Central South University, from January 1, 2016, to December 31, 2020 were retrospectively analyzed. Of the patients, 196 cases underwent laparoscopic hepatectomy (laparoscopic group), and 321 patients underwent open hepatectomy (open surgery group). The general data, perioperative conditions, and follow-up results were analyzed and compared between the two groups of patients.Results In terms of general data, there were statistically significant differences between the laparoscopic group and the open surgery group in tumor stage, tumor diameter, preoperative albumin level, and site of liver resection (all P<0.05), while the remaining differences were not statistically significant (all P>0.05). In perioperative variables, the laparoscopic group showed better outcomes than the open surgery group in terms of median intraoperative blood loss (200.00 mL vs. 300.00 mL), median length of postoperative hospital stay (6 d vs. 8 d), postoperative liver function recovery, and incidence of postoperative complications (6.63% vs. 14.02%), all of which were statistically significant (all P<0.05). Regarding follow-up results, the laparoscopic group had superior overall survival (OS) and disease-free survival (DFS) compared to the open surgery group (OS: χ²=4.478, P=0.034; DFS: χ²=8.915, P=0.003). After balancing the general data of the two groups through propensity score matching (1∶1 matching, 51 cases in each group), the laparoscopic group still showed better postoperative hospital stay (6 d vs. 9 d) and incidence of postoperative complications (3.92% vs. 19.61%) than those in the open surgery group, but there was no statistically significant difference in OS and DFS between the two groups (both P>0.05).Conclusion Laparoscopic hepatectomy for HCC is safe and effective, which can accelerate postoperative recovery and reduce postoperative hospital stay. The long-term efficacy of laparoscopic and open hepatectomy for HCC is comparable. Laparoscopy has its own indications, and after comprehensive evaluation of patients, laparoscopic surgery should be the preferred surgical approach for HCC patients.