Background <p>Pneumonia is a common cause of morbidity and mortality, with severe cases often progressing to complications such as sepsis and respiratory failure. Early diagnosis and intervention are crucial for improving outcomes. MicroRNAs (miRNAs) have been identified as potential biomarkers for various diseases, including pneumonia. This study aimed to evaluate the potential role of miR-6822-3p as a diagnostic and prognostic biomarker in severe pneumonia and to explore its underlying mechanisms.</p> Methods <p>The GSE153131 dataset from the GEO database was analyzed to identify differentially expressed miRNAs. Serum samples from 70 mild pneumonia patients, 70 severe pneumonia patients, and 70 healthy controls were used to validate miR-6822-3p expression. In vitro experiments using A549 and THP-1 cells were conducted to investigate the role of miR-6822-3p in inflammation and pyroptosis.</p> Results <p>miR-6822-3p was significantly upregulated in severe pneumonia patients and showed potential as a diagnostic biomarker. In vitro studies revealed that miR-6822-3p promoted inflammation and pyroptosis. High miR-6822-3p expression was associated with poorer clinical outcomes, including lower 28-day survival rates.</p> Conclusions <p>miR-6822-3p may be a potential diagnostic and prognostic biomarker for severe pneumonia. Further studies are needed to validate its clinical utility and explore its therapeutic potential.</p>