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Retrospective studies report that the benefit of regional anesthesia on cancer recurrence may depend on the specific tumor type. We compared the association between anesthetic technique and cancer recurrence in patients undergoing percutaneous radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC).We retrospectively reviewed medical records of patients with small HCC treated with RFA between August 1999 and December 2008. Patients receiving epidural anesthesia were compared with a group given general anesthesia. The end points were recurrence-free survival and overall survival, which were assessed using the Kaplan-Meier technique and compared using a multivariate Cox proportional hazards regression model and an alternative model with inverse probability weights to adjust for propensity score.The hazard ratio for recurrence-free survival in the epidural anesthesia group compared with the general anesthesia group was 3.66 (95% confidence interval [CI], 2.59–5.15; P < 0.001) in the Cox regression model and 4.31 (95% CI, 2.24–8.29; P < 0.001) in the analysis adjusted for propensity score with inverse probability weights. The hazard ratio for overall survival in the epidural anesthesia group compared with the general anesthesia group was 0.77 (95% CI, 0.50–1.18; P = 0.232) in the Cox regression model and 1.26 (95% CI, 0.81–1.97; P = 0.312) in the analysis adjusted for propensity score with inverse probability weights.This retrospective analysis suggests that treatment of small HCC by RFA under general anesthesia is associated with reduced risk of cancer recurrence. No effect of anesthetic technique on overall survival is detected. Prospective, randomized trials to evaluate this association are warranted.