Background Nucleic acid is a genetic material that shows great potential in a variety of biological applications. With the help of nanotechnology, the fabrication of DNA-based nanomaterials has emerged. From genetic DNA to non-genetic functional DNA, from single-layer and flat structure to multi-layer and complex structure, and from two-dimensional to three-dimensional structure, DNA-based nanomaterials have been greatly developed, bringing significant changes to our lives. In recent years, the research of DNA-based nanomaterials for biological applications has developed rapidly.Methods We extensively searched the bibliographic database for a research article on nanotechnology and immunotherapy and further discussed the advantages and drawbacks of current DNA-based nanomaterials in immunotherapy. By comparing DNA-based nanomaterials with traditional biomaterials applied in immunotherapy, we found that DNA-based nanomaterials are a promising candidate material in Immunotherapy.Results Due to the unrivaled editability and biocompatibility, DNA-based nanomaterials are not only investigated as therapeutic particles to influence cell behavior but also as drug delivery systems to treat a variety of diseases. Moreover, when DNA-based nanomaterials are loaded with therapeutic agents, including chemical drugs and biomolecules, which significantly enhance the therapeutic effects, DNA-based nanomaterials have great potential in immunotherapy.Conclusion This review summarizes the structural development history of DNA-based nanomaterials and their biological applications in immunotherapy, including the potential treatment of cancer, autoimmune diseases, and inflammatory diseases.