Aim: We wanted to assess the potency of a trifunctional nanoparticle (NP) that targeted and activated CD8⁺ dendritic cells (DC) and delivered an antigen to induce antitumor responses. Materials & methods: The DC targeting and activating properties of ferrous NPs conjugated with immunostimulatory CpG-oligonucleotides, anti-DEC205 antibody and ovalbumin (OVA) as a model antigen to induce antigen-specific T-cell responses and antitumor responses were analyzed. Results: OVA-loaded NP conjugated with immunostimulatory CpG-oligonucleotides and anti-DEC205 antibody efficiently targeted and activated CD8⁺ DC in vivo, and induced strong OVA-specific T-cell activation. Vaccination of B16/OVA tumor-burdened mice with this NP formulation resulted in tumor growth arrest. Conclusion: CD8⁺ DC-targeting trifunctional nanocarriers bear significant potential for antitumor immunotherapy.