Autoimmune thyroid disease (AITD) is the typical organ-specific autoimmune disorder. However, the underlying molecular mechanisms by which immune reactions against specific thyroid proteins are induced are still largely unknown. Accumulated evidence from animal models has generated new insights into the pathogenesis of AITD. Recent studies have indicated that innate immune responses induced by both exogenous and endogenous factors affect the phenotype and severity of autoimmune reactions. One of the recent topics is the effect of self genomic DNA fragments on immune activation. Here we review by focusing on the possible role of innate immune activation in the development of AITD.