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Radiofrequency ablation (RFA) is a promising tumor treatment in clinics, but its use is limited given the high post-RFA recurrence rate. To overcome tumor relapse, RFA needs to be used in combination with a long-lasting treatment. Obviously, the focal injection of antitumor drugs is capable of increasing the effective treatment period. Nano drug delivery systems (NDDS), which allow for a controlled and slow release of drugs, provide a promising strategy to overcome post-RFA tumor recurrence. Our results showed a clear transit area, between the non-ablation tumor area and the ablation necrotic area, indicative of apparent histopathological partition. Focal injection of the NDDS in combination with focally-injected carbomicin (CBMC) is an effective assistant treatment for RFA, as it increases efficiency and inhibits tumor relapse. Focally injected CBMC is a novel strategy which overcomes the disadvantages of RFA and may even cure it.