Background <p>As a predominant driver of pediatric mortality, severe pediatric pneumonia (SPP) is an important complication to be solved. The miR-1271-5p is universally engaged in pulmonary infection. This study focused on miR-1271-5p for the first time and aimed to reveal its role in SPP.</p> Methods <p>The study enrolled 268 children aged 2–10 years, comprising 81 healthy individuals and 187 with pneumonia. The expression level of serum miR-1271-5p was assessed by qRT-PCR. The receiver characteristic (ROC) curve was employed to distinguish pneumonia children from healthy controls. Multivariate logistic regression analyzed factors associated with progression from mild-moderate pneumonia to SPP. Multivariate Cox regression assessed the association of miR-1271-5p expression with poor prognosis, and the Kaplan-Meier survival curve was subsequently generated based on miR-1271-5p levels.</p> Results <p>Serum miR-1271-5p levels were remarkably elevated in children with pneumonia, especially SPP. Importantly, miR-1271-5p showed high diagnostic value of SPP, with the AUC of 0.877, the sensitivity of 74.9% and specificity of 87.8%. The results of multivariate logistic analysis demonstrated that miR-1271-5p was an independent risk factor for progression to SPP. Elevated serum miR-1271-5p levels were associated with poor prognosis in children with pneumonia and possessed predictive value for patients’ adverse outcomes.</p> Conclusion <p>Elevated serum miR-1271-5p was demonstrating superior diagnostic and prognostic specificity in severe pediatric pneumonia, providing a potential biomarker.</p>