Background <p>High mortality of pediatric acute respiratory distress syndrome (PARDS) demands new biomarkers.</p> Aim <p>The study aims to clarify the clinical value of miR-192-5p in PARDS and its regulatory role in inflammatory responses.</p> Methods <p>Baseline data and serum samples were collected from healthy children, sepsis children, and sepsis-induced PARDS subjects. The receiver operating characteristic curve (ROC), Kaplan-Meier curve and multivariate Cox regression were used to assess miR-192-5p’s diagnostic and prognostic value for PARDS. The relationship between miR-192-5p and each index was evaluated by correlation analysis. The expression of miR-192-5p, inflammatory factors and ZEB2 in the subjects’ serum and human pulmonary microvascular endothelial cells (HPMECs) were detected by RT-qPCR. The cell viability and secretion of inflammatory factors were evaluated by CCK-8 and ELISA kit. Bioinformatic prediction combined with dual-luciferase reporter assay was used to verify the target genes.</p> Results <p>miR-192-5p was significantly low-expressed in PARDS patients’ serum. MiR-192-5p was a prognostic protective factor for PARDS, and low miR-192-5p indicated poor prognosis. MiR-192-5p was negatively correlated with TNF-α, IL-6, IL-1β, and APACHE II score. LPS treatment led to reduced HPMECs viability, excessive inflammatory factor production, and down-regulated miR-192-5p expression. Overexpression of miR-192-5p mimic could partially reverse the above phenomena, while knockdown could aggravate the above phenomena. ZEB2 was a downstream target gene of miR-192-5p.</p> Conclusions <p>miR-192-5p serves as a diagnostic biomarker for PARDS and links to poor prognosis. Downregulation of miR-192-5p may promote LPS-induced inflammatory response and induce HPMECs cell viability by targeting ZEB2, thereby involving in the progression of PARDS.</p>