BX-912 and Navitoclax can be considered drug screening strategies for the treatment of ESCC patients by targeting PRKDC and SLC25A13.<h4>Conclusion</h4>cGAS-STING pathway can guide risk stratification and can be considered as a therapeutic target for ESCC patients, which provides novel insights into precision and personalized medicine for ESCC patients. Here, PRKDC is linked to esophageal squamous cell carcinoma.