The well-designed activation of dendritic cells (DCs) by enhancing the delivery of antigens and immunostimulatory adjuvants into DCs is a key strategy for efficient cancer immunotherapy. Antigen-antibody immune complexes (ICs) are known to directly bind to and cross-link Fc-gamma receptors (Fc gamma Rs) on DCs, which induce enhanced migration of DCs to draining lymph nodes through the up-regulation of the chemokine receptor CCR7 and cross-presentation inducing cytotoxic T lymphocyte (CTL) response against tumor antigen. In this study, ICs mimicking synthetic vaccine nanoparticles (NPs) are designed and synthesized by the coating of poly (lactic-co-glycolic acid) (PLGA) NPs containing adjuvant (CpG oligodeoxynuleotides (ODNs) as toll-like receptor 9 ligands) with ovalbumin (OVA) proteins (as model antigens) and by the formation of OVA-OVA antibody ICs. Through the combination of Fc gamma Rs-mediated efficient antigen uptake and CpG ODNs-based immunostimulation, the secretion of TNF-alpha (12.3-fold), IL-6 (7.29-fold), and IL-12 (11-fold), homing ability to lymph nodes (7.5-fold), and cross-presentation (83.8-fold IL-2 secretion) are dramatically increased in DCs treated with PLGA(IC/CpG) NPs. Furthermore, mice vaccinated with DCs treated with PLGA(IC/CpG) NPs induced significant tumor (EG7-OVA) growth inhibition as well as prolonged survival through CTL-mediated enhanced cytotoxicity, antigen-specific responses, and IFN-gamma secretion.