The enhancement of immune response against tumor antigens has shown some efficacy when used as a single mode of systemic treatment in patients with late stage disease. Novel strategies of active immunotherapy could be more effective in patients with less advanced disease who receive standard therapies supporting concomitant stimulation of the immune system. Radio-Frequency Ablation (RFA) is a minimally invasive technique which is used as standard local therapy of primary and metastatic liver tumors. Tumor ablation by RFA induces effects important for boosting anti-tumor immune responses. Tumor cell necrosis generates a permanent immunogenic source of tumor antigens. These antigens can be uptaken, processed and presented by dendritic cells for effective immunization without requirement for ex vivo antigen loading. Further immune activation can be originated by RFA through induction of heat shock proteins on tumor cells, acute phase response which causes the release of pro-inflammatory cytokines, and mobilization of antigen presenting cells and effector lymphocytes. Thus, RFA can facilitate immune responses to tumor antigens driven by active immunotherapy. On the other hand, immunotherapy is expected to eradicate residual disease after RFA and prevent tumor recurrences. The combination of RFA and active immunotherapy may well have synergistic effects for cancer treatment.