The cyclic guanosine monophosphate‒adenosine monophosphate synthase (cGAS)‒mediator of interferon response factor 3 activation/stimulator of interferon genes (MITA/STING) axis has emerged as a major pathway, which senses microbial or mislocated cellular DNA in the cytosol to trigger innate immune responses. cGAS senses cytosolic DNA without a preference of self- or nonself-DNA. How the cGAS‒MITA/STING axis is inactivated upon nuclear envelope breakdown (NEBD) at mitotic entry in vertebrate cells to avoid self-DNA sensing remains unclear until very recently. In this review, we summarize the recent advances on how cGAS responds to chromosomes upon NEBD and the mechanisms involved in the inactivation of the cGAS‒MITA/STING pathways in mitosis.