Background <p>Severe pneumonia (SP) is a critical infectious disease characterized by excessive inflammatory responses, and the molecular mechanisms underlying its progression remain incompletely understood.</p> Objective <p>To investigate the expression pattern, diagnostic value, and potential functional regulatory mechanisms of miR-200b in SP.</p> Methods <p>RT-qPCR was used to detect miR-200b expression levels; ROC curve analysis was used to evaluate its diagnostic performance; prognostic indicators of miR-200b were compared between high- and low-expression groups, and Cox regression was employed to identify independent prognostic factors. In vitro validation of the pro-inflammatory effects of miR-200b. Target genes were identified through Venn diagram-based prediction and dual luciferase reporter assays. Functional recovery experiments were conducted to elucidate regulatory pathways.</p> Result <p>miR-200b expression was significantly higher in SP patients than in CP/HC groups, with an ROC curve AUC of 0.848 distinguishing SP from CP/HC, demonstrating good diagnostic performance. Elevated miR-200b expression significantly correlated with poorer prognostic indicators and served as an independent risk factor for adverse SP outcomes. In vitro experiments demonstrated that miR-200b expression was upregulated in a concentration- and time-dependent manner following LPS stimulation, promoting IL-6 and TNF-α secretion. RHOA was identified as a direct target gene of miR-200b, and miR-200b exerts pro-inflammatory effects by inhibiting RHOA and activating the NF-κB pathway.</p> Conclusion <p>miR-200b serves as a potential diagnostic and prognostic biomarker for SP. By targeting RHOA to activate the NF-κB pathway, it promotes inflammatory damage in SP, thus providing a novel therapeutic target for clinical intervention.</p>