Tumor size (HR = 1.27, 95% CI: 1.15–1.40), HBV-DNA (HR = 7.70, 95% CI 3.57–16.63), AFP levels before treatment (HR = 2.172, 95% CI 1.256–3.756, P = 0.006), 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. The gene discussed is AFP; the disease is hepatocellular carcinoma.