Objective To investigate the expression of serum long non-coding RNA MEG3 and microRNA(miR)-195-5p in patients with severe necrotizing pancreatitis and their relationship with the severity and prognosis of severe necrotizing pancreatitis.Methods A total of 122 patients with acute pancreatitis admitted to Cangzhou Central Hospital from October 2020 to January 2023 were selected as the research objects.Ac-cording to the severity of the disease,the patients were divided into severe necrotizing pancreatitis(severe group,53 cases)and non-severe necrotizing pancreatitis(non-severe group,69 cases).According to the prog-nosis of alternate ending with severe necrotizing pancreatitis can be divided into good prognosis group(38 ca-ses)and poor prognosis group(15 cases).At the same time,50 healthy people who underwent physical exami-nation in the hospital during the same period were selected as the control group.The clinical data and serum levels of lncRNA MEG3 and miR-195-5p in each group were compared.Spearman correlation analysis was used to analyze the relationship between serum levels of lncRNA MEG3,miR-195-5p and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)and Ranson scores.Multivariate Logistic regression was used to analyze the influencing factors of poor prognosis in patients with severe necrotizing pancreatitis.The receiver operating characteristic(ROC)curve was used to analyze the value of lncRNA MEG3 and miR-195-5p in eval-uating the prognosis of patients with severe necrotizing pancreatitis.Results There was no significant differ-ence in age,gender,body mass index,underlying disease and etiology between severe group and non-severe group(P>0.05).Compared with the non-severe group,APACHEⅡ and Ranson scores were significantly in-creased in the severe group(P<0.05).Compared with the control group,the serum levels of lncRNA MEG3 and miR-195-5p in the non-severe group and the severe group were decreased(P<0.05),and the serum levels of lncRNA MEG3 and miR-195-5p in the severe group were lower than those in the non-severe group(P<0.05).Spearman correlation analysis showed that serum levels of lncRNA MEG3 and miR-195-5p in AP pa-tients were negatively correlated with APACHEⅡ and Ranson scores(P<0.05).Multivariate Logistic re-gression analysis showed that APACHEⅡ and Ranson scores and serum levels of lncRNA MEG3 and miR-195-5p were independent risk factors for poor prognosis in patients with severe necrotizing pancreatitis(P<0.05).ROC curve results showed that the area under the curve(AUC)of lncRNA MEG3 and miR-195-5p for evaluating the poor prognosis of patients with severe necrotizing pancreatitis was 0.767 and 0.777,respectively,the sensitivity was 86.7%and 80.0%,and the specificity was 49.9%and 45.8%,respectively.The AUC of combined e-valuation was 0.982,and the sensitivity and specificity were 86.7%and 78.8%,respectively.Conclusion The serum levels of lncRNA MEG3 and miR-195-5p are related to the severity and prognosis of severe necrotizing pancreatitis,which can evaluate the severity and predict the prognosis of severe necrotizing pancreatitis.