Abstract: OBJECTIVE To evaluate the value of miR-136 in predicting the severity of gastric mucosal lesions and the risk of gastric cancer after Helicobacter pylori (Hp) infection. METHODS A prospective study was conducted on 609 patients with chronic gastritis who visited the Gastroenterology Department of Xuzhou Central Hospital from Jan. 2019 to Dec. 2024. The severity of chronic gastritis was classified with the OLGA/OLGIM staging system, and patients were divided into two groups: OLGA/OLGIM stage I-II and OLGA/OLGIM stage III-IV. All subjects underwent serum miR-136 detection, Hp detection and questionnaire survey. Differences in demographic and clinical characteristics, miR-136 expression and Hp infection rate between the two groups were compared. Univariate and multivariate logistic regression analyses were performed to identify risk factors for OLGA/OLGIM. Ⅲ-Ⅳ stage Hp eradication therapy and follow-up were administered to all patients included in the study. The area under the curve was used to evaluate the predictive ability of miR-136 for OLGA/OLGIM staging of gastric mucosal lesions after Hp infection and the risk of gastric cancer development. RESULTS Patients with OLGA/OLGIM stages III-IV exhibited higher serum miR-136 expression levels and Hp infection rates than those with OLGA/OLGIM stages I-II. Logistic regression analysis indicated that high expression of miR-136 and Hp infection were independent risk factors for OLGA/OLGIM stages III-IV. Follow-up surveys revealed that all nine patients with chronic gastritis who progressed to gastric cancer were in OLGA/OLGIM stages III-IV, seven had failed eradication, and two had converted to negative after eradication. The area under the curve for serum miR-136 in OLGA/OLGIM stages III-IV with positive and negative Hp infection was (0.813, 0.786), respectively. CONCLUSION Serum miR-136 is helpful in assessing the severity of chronic gastritis after Hp infection and early screening for the risk of gastric cancer.