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Purpose: To evaluate the effect of using intravenous injection of omeprazole to prevent stress-related mucosal damage (SRMD) in critically ill patients. Methods: 80 critically ill patients from the Eighth People's Hospital of Qingdao, Qingdao, China were recruited and randomly divided into control and study groups comprising 40 patients each. Control group received conventional symptomatic treatment comprising nutritional support, acid-base balance regulation, electrolyte level monitoring and correction, maintenance of fluid and electrolyte equilibrium, respiratory function management, and anti-infection measures. Study group received intravenous injection of omeprazole (20 mg/day) and conventional symptomatic treatment for 3 months. Treatment effect, gastric pH, and gastroscopic observation of the two groups of patients were recorded. Results: The study group demonstrated significantly higher treatment efficacy (97.5 %) compared to control group (80 %, p < 0.05). Pre-treatment gastric pH did not differ significantly between the groups (p > 0.05). After treatment, the study group exhibited significantly higher pH levels (p < 0.05). Normal endoscopic findings increased to 85 % in the study group compared to 20 % in control group (p < 0.05). Conclusion: Intravenous omeprazole significantly prevents SRMD in critically ill patients, improves gastric pH regulation and reduces abnormal endoscopic findings. Larger-scale, multicenter, and longterm studies are needed to validate the findings of this study. [ABSTRACT FROM AUTHOR]