The objective of this study was to investigate the long-term outcomes between laparoscopic anatomical liver resection (LAR) and laparoscopic non-anatomical liver resection (LNAR) in patients with hepatocellular carcinoma (HCC).In this single-center retrospective cohort study, 1773 patients, from January 2009 to December 2017, were assessed for inclusion. After exclusions, 661 patients were included: 304 patients received LAR and 357 patients received LNAR. Propensity score matching (PSM) with 1:1 ratio was used to eliminate the selection bias between LAR and LNAR groups. The Kaplan-Meier and Cox models were used for survival analysis.After PSM, 250 patients were in LAR or LNAR group, respectively. The overall survival (OS) had no significant difference between LAR and LNAR by Kaplan-Meier analysis. While, LAR had better disease-free survival (DFS) compared with LNAR (Log-rank P=0.035). The cumulative 5-year DFS rates were 48% for LAR, and 38% for LNAR. By Cox analysis, LAR was an independent risk factor of DFS (HR=1.308, P=0.030). In subgroup analysis for tumor size ≤ 5 cm, 207 patients were in LAR or LNAR subgroup after PSM. LAR had better DFS compared with LNAR (Log-rank P=0.033). LAR was an independent risk factor of DFS (HR=1.333, P=0.036). The cumulative 5-year DFS rates were 50% for LAR, and 39% for LNAR. In another subgroup analysis for tumor size > 5 cm, 43 patients were in LAR or LNAR subgroup after PSM. The DFS had no significant difference between LAR and LNAR (Log-rank P=0.912).LAR is preferred for HCC patients with tumor size ≤5cm compared with LNAR because of the better DFS. For patients with tumor size >5cm, LAR and LNAR might be alternative procedures with comparable long-term outcomes.© 2024 Leng et al.