Abstract: Objective To compared the efficacy of laparoscopy- assisted radiofrequency ablation (LRFA) and percutaneous radiofrequency ablation (PRFA) for the treatment of hepatocellular carcinoma (HCC). Methods Between September, 2013 and September, 2016, a total of 60 HCC patients with 78 tumor nodules underwent LRFA (30 cases with 46 tumor nodules) and PRFA (30 cases with 32 tumor nodules) in our hospital. The patients were followed up for 3 years to compare the complete ablation rate, serious complications, recurrence rate and long-term survival rate between the two groups. Results The patients receiving LRFA had a complete ablation rate of 95.65% (44/46), significantly higher than the rate of 93.75% (30/32) in PRFA group (P>0.05). Significant differences were found between LRFA and PRFA groups in the incidence of serious complications [0 vs 6.7% (2/30), P<0.05] and recurrence rate [13.33% (4/30) vs 23.33% (7/30), P<0.05]. The 1-and 3-year overall survival rates of the patients were 96.15% and 55.12% in LRFA group and 93.73% and 48.54% in PRFA group, respectively (P>0.05). Conclusions Both LRFA and PRFA are effective for HCC treatment, but is associated with a lower recurrence rate, fewer serious complications, a better treatment safety and a better applicability for tumor in difficult locations.