【Abstract】Objective：This study aims to investigate the function and mechanism of cGAS-STING pathway in acid and deoxycholic acid induced human esophageal epithelial cell inflammation. Methods：HEECs were cultured in vitro. The viability of cells treated with acid and DCA was measured by CCK8 assay. The effects of drugs on cell morphology were observed by optical microscope. Changes of cellular reactive oxygen species, mitochondrial reactive oxygen species，mitochondrial membrane potential were detected by fluorescence microscope and flow cytometry. ATP was detected by the kit. The ultrastructure of mitochondria was observed by transmission electron microscope. The expression of γH2AX was detected by immunofluorescence and Western blotting. The colocalization of mitochondria and DNA was detected by immunofluorescence. The mtDNA copy number was evaluated by qPCR. The expressions of cGAS、STING、p-NF-κB p65 and NF-κB p65 were detected by Western blotting. The mRNA expressions of inflammatory cytokines IL-6 and IL-1β were detected by qPCR. Results: CCK8 assay showed that acid and DCA inhibited the viability of HEECs in a concentration- and time- dependent manner. Intracellular ROS and mtROS were increased after drug treatment, along with reduced MMP and ATP. The expression of γH2AX was elevated. Compared with the negative control group，the expression of γH2AX was increased after acid and DCA stimulation, mtDNA released into the cytoplasm, mtDNA copy number was reduced, the expressions of cGAS, STING and p-NF-κB p65 were increased, and the expressions of inflammatory cytokines IL-6 and IL-1β were elevated. After treatment with cGAS inhibitor RU.521, the expression levels of cGAS and STING were inhibited and the expression of p-NF-κB p65 was partially inhibited, and the levels of inflammatory cytokines IL-6 and IL-1β were decreased. Conclusion: Acid and DCA can induce mitochondrial dysfunction, mtDNA release and mediate the inflammation of HEEC, which may be associated with the activation of cGAS-STING pathway.