Dendritic cells (DCs) are crucial immune cells detecting microorganisms and linking innate and adaptive immunity. Various microorganism-derived components, including lipids, proteins, or nucleic acids, activate DCs through various pattern recognition receptors (PRRs). PRRs can principally detect non-self-components, but nucleic acid components are peculiar in that self-derived nucleic acids can also stimulate PRRs. Thus, nucleic-acid-sensing PRRs can potentially cause autoimmune responses. This potential danger comes out in certain situations, and especially nucleic-acid-induced type I interferon production contributes to the pathogenesis of autoimmune disorders. Here we review how DCs detect and respond to nucleic acid adjuvants and how self-derived nucleic acids can cause autoimmunity. Clarifying such mechanisms should contribute to the development of therapeutic manipulation for autoimmune diseases.