The multivariate analysis showed that tumor size (HR = 1.27, 95% CI 1.15–1.40, P = 0.0001) and HBV-DNA levels (HR = 7.70, 95% CI 3.57–16.63, P = 0.0001), AFP levels before treatment (HR = 2.172, 95% CI 1.256–3.756, P = 0.0055), and AFP response (HR = 4.722, 95% CI 1.053–21.184, P = 0.0427) were independently associated with the risk of recurrence of HCC after RFA. Here, AFP is linked to neoplasm.