Cyclic GMP-AMP synthase (cGAS) is a critical intracellular sensor that can recognize abnormally located DNA in the cytoplasm and trigger immune responses. We successfully cloned and analyzed Crassostrea gigas cGAS (CgcGAS) to reveal its significant role in the innate immune regulation of mollusks. The open reading frame (ORF) of CgcGAS gene was 1623 bp and encoded 540 amino acids with a theoretical molecular weight of 62.3 kD and a conserved Mab21 domain. Phylogenetic analysis supported the traditional morphological classification and indicated a close evolutionary relationship between CgcGAS and other shellfish cGAS genes, confirming its status as a member of the molluscan cGAS family. The expression pattern of cGAS in Crassostrea gigas was determined, which was widely expressed in various tissues, with the highest relative expression level found in digestive glands, providing a basis for further research on the role of cGAS in oyster physiology. Subsequently, CgcGAS was observed in both the nucleus and cytoplasm, suggesting that CgcGAS may have played a role in DNA sensing in the nucleus and DNA binding and signaling in the cytoplasm. Furthermore, we demonstrated that CgcGAS could activate the NF-κB and ISRE signaling pathways, as well as the expression of downstream inflammation-related factors such as viperin, IRF2/8, TNF, and IL-17. These results demonstrated the critical role of CgcGAS in regulating the innate immune response of Crassostrea gigas.