Cytosolic nucleic acid sensors are critical for sensing nucleic acids and initiating innate immunity during microbial infections and/or cell death.Over the last decade,several key studies have characterized the conserved mechanism of cyclic guanosine mo-nophosphate-adenosine monophosphate synthase (cGAS) and the downstream signaling adaptor stimulator of interferon genes(STING) initiating the innate immune signaling pathways.Aside from its primary involvement in microbial infections and inflam-matory diseases,there is growing interest in the alternate roles of cGAS-STING-mediated signaling.Caspase family members are powerful functional proteins that respond to cellular stress,including cell death signals,inflammation,and innate immunity.Recent studies have uncovered how the caspase family cooperates with the cGAS-STING signaling pathway.Most caspase family members negatively regulate the cGAS-STING signaling pathway.In turn,some caspase family members can also be modulated by cGAS-STING.This review gives a detailed account of the interplay between the caspase family and the cGAS-STING signaling pathway,which will shed light on developing novel therapeutics targeting the caspase family and cGAS-STING signaling in anti-viral innate immunity,cancer,inflammatory,and autoimmunity.