Radiofrequency ablation (RFA) is the best choice for curative treatment of hepatocellular carcinoma (HCC) cases not suitable for surgical intervention, but efforts should be made to reduce the risk of tumor recurrence. We aimed to investigate the association between nucleos(t)ide analogue (NA) therapy for hepatitis B virus (HBV) and the risk of HCC recurrence following RFA. Using the Taiwan National Health Insurance Research Database between July 1, 2004 and December 31, 2012, we screened 48,807 patients with newly diagnosed HBV-related HCC. We identified 850 patients (200 patients who used NAs for more than 90 days and 650 patients who never used NA after RFA) who received RFA as a potentially curative treatment for HCC. Patients in the NA-treated cohort were randomly matched 1:2 with patients in the untreated cohort by age, gender, cirrhosis, and the time period between RFA and initiation of NA therapy. Finally, 133 patients were recruited in the NA-treated group and 266 in the untreated group for analysis. Cumulative incidences of and hazard ratios (HRs) for HCC recurrence were analyzed after adjusting for competing mortality. The HCC recurrence rate of the NA-treated group was significantly lower than that of the untreated group (2-year recurrence rate: 41.8%, 95% confidence interval [CI]: 32.9-50.6% vs. 54.3%, 95% CI: 48.0-60.6%; modified log-rank test P< 0.05). In modified Cox regression analysis, NA therapy was independently associated with a decreased risk of HCC recurrence (HR 0.69, 95% CI: 0.50-0.95; P< 0.05). Multivariate stratified analyses verified the association of NA therapy and decreased HCC recurrence in almost all patient subgroups. CONCLUSION: NA therapy was associated with a decreased risk of HCC recurrence among patients with HBV-related HCC following RFA.