BACKGROUND Treatment outcomes of laparoscopic liver resection (LLR) and percutaneous radiofrequency ablation (p-RFA) for small single hepatocellular carcinomas (HCCs) have not yet been fully compared. The aim of this study was to compare LLR and p-RFA as first-line treatment options in patients with single nodular HCCs ≤3 cm. METHODS From January 2014 to December 2016, a total of 566 patients with single nodular HCC ≤3 cm treated by either LLR (n = 251) or p-RFA (n = 315) were included. The recurrence-free survival (RFS) and cumulative incidence of local tumor progression (LTP) were estimated using Kaplan-Meier methods and compared using the log-rank test. Treatment outcome of 2 treatment modalities was compared in the subgroup of patients according to the tumor location. RESULTS There were no significant differences in overall survival between LLR and p-RFA (p = 0.160); however, 3-year RFS was demonstrated to be significantly higher after LLR (74.4%) than after p-RFA (66.0%) (p = 0.013), owing to its significantly lower cumulative incidence of LTP (2.1% at 3 years after LLR vs. 10.0% after p-RFA, p < 0.001). The complication rate of p-RFA was significantly lower than that of LLR (5.1 vs. 10.0%, p = 0.026). LLR also provided significantly better local tumor control than p-RFA for subscapular tumors (3-year LTP rates: 1.9 vs. 8.8%, p = 0.012), perivascular tumors (3-year LTP rates: 0.0 vs. 17.2%, p = 0.007), and tumors located in anteroinfero-lateral liver portions (3-year LTP rates: 0.0 vs. 10.7%, p < 0.001). However, there were no significant differences in LTP rates between LLR and p-RFA for non-subcapsular and non-perivascular tumors (p = 0.482) and for tumors in postero-superior liver portions (p = 0.380). CONCLUSIONS LLR can provide significantly better local tumor control than p-RFA for small single HCCs in subcapsular, perivascular, and anteroinferolateral liver portions and thus may be the preferred treatment option for these tumors.