We explored two feasible translational directions for DHX58: as a predictive biomarker, its liquid biopsy-detectable methylation status may improve GC immunotherapy response prediction accuracy; as a therapeutic target, inhibiting the CEBPα-DHX58 axis (e.g., via CEBPα small-molecule inhibitors or DHX58 siRNA) may reverse the tumor microenvironment’s immunosuppressive state. The gene discussed is CEBPA; the disease is neoplasm.