STING (stimulator of interferon genes) is an essential signaling adaptor that mediates cytokine production in response to microbial invasion by directly sensing bacterial secondary messengers such as the cyclic dinucleotide bis-(3'-5')-cyclic dimeric GMP (c-di-GMP). STING's structure and its binding mechanism to cyclic dinucleotides were unknown. We report here the crystal structures of the STING cytoplasmic domain and its complex with c-di-GMP, thus providing the structural basis for understanding STING function.