In the patients whose all three tumor markers (AFP, AFP‐L3, and DCP) had increased after successful RFA (n = 9), intra‐ and extrasubsegmental recurrence for HCC were significantly higher than the other patients (subsegmental recurrence: HR = 3.91; 95% CI = 1.68–9.10; P = 0.002 and extrasubsegmental recurrence: HR = 2.33; 95% CI = 1.04–5.21; P = 0.040). This evidence concerns the gene AFP and hepatocellular carcinoma.