Objective To study the therapeutic effect of somatostatin combined with omeprazole in patients with severe acute pancreatitis (SAP) and its influence on inflammatory factors [high-sensitivity C-reactive protein (hs-CRP), interleukin-8 (IL-8)]. Methods: Seventy-two cases of SAP patients in our hospital were selected as the subjects of this experiment, and the cases were collected from March 2020 to February 2024, and were divided into 36 cases of single-administration group (treated with omeprazole) and 36 cases of combined-administration group (treated with growth inhibitor on the basis of single-administration group) according to the different therapeutic drugs. The efficacy of the two groups, the levels of inflammatory factors (hs-CRP, IL-8) before and after treatment, the time to improve clinical symptoms and the incidence of adverse reactions were compared. Results: The total effective rate of 97.22% (35/36) was higher in the combination group than 75.00% (27/36) in the single-administration group (P < 0.05); compared with the single-administration group, the levels of hs-CRP and IL-8 were lower in the combined-administration group after treatment (P < 0.05); compared with the single-administration group, the relief of abdominal pain, recovery of gastrointestinal function, and the time of disengagement from respiratory machine were shorter in the combined-administration group (P <0.05); there was no significant difference between 2 cases (5.56%) of adverse reactions in the combination group compared with 4 cases (11.11%) in the single-drug group (P>0.05). Conclusion: Growth inhibitor combined with omeprazole is effective in the treatment of SAP, which can significantly reduce the levels of hs-CRP, IL-8 and other inflammatory factors, protect the intestinal barrier function, and promote the improvement of symptoms, and the safety of the combination of drugs is good.