The innate immune system may be the first defence line to detect and counter viral and microbial invasion. There are many mechanisms working in innate system, which would be helpful to understand the pathogenesis of infectious diseases, virus-related cancers and autoimmune diseases. Despite of the understanding about the recognition signaling in response to cellular RNA, the recognition mechanisms and related innate immunological response of pathogen DNA still remain largely unclear. Recently, a few molecules in the cell were discovered to function as DNA sensors which play key roles during DNA mediated IFN production. Besides, some molecules that could regulate IFN signaling were isolated and shown to be critical for DNA mediated innate immunity. Recent progress about the detection and recognition of pathogenic DNA, as well as its regulation of innate immunity were summarized.