The intracellular DNA sensors in host cells recognize viral nucleic acid and activate the innate immunity, then resulting in antiviral effects. However, the viral pathogens have also evolved with appropriate strategies to evade or suppress the innate immune responses. In this review, the characteristics and molecular mechanisms of the immune effects of PYHIN family, one of the DNA sensors in host cells that could recognize viral DNA and activate innate immunity are discussed. The strategies of how viruses escape from the immune surveillance are also summarized.