Although there has been significant progress in the development of tumor immunotherapies, many challenges still exist for the treatment of solid tumors. Natural killer (NK) cells possess broad-spectrum cytotoxicity against tumors, but their limited migration and infiltration abilities restrict their application in solid tumor therapies. Here, we combined a facile and efficient magnetic-targeting strategy with NK cell-based therapy to develop a novel immunotherapy approach for treating solid tumors. Anti-CD56 antibodies were conjugated with Fe3O4 nanoparticles, which could specifically bind with NK-92 cells endowing them with a magnetic field driven targeting ability. These NK-Fe3O4 biohybrid nanoparticles were able to facilitate directional migration to the tumor site in vivo under external magnetic field guidance and efficiently inhibit tumor growth. These functionalized NK cells represent a novel approach for solid tumor therapy and may provide a promising modality for cancer interventions in the future.