 In this study, we found that mere 146a5p delivered by extracellular vesicles derived from human umbilical cord mesenchymal stromal cells, HUC-MSCEVS, could exert therapeutic effects on sulfur mustard, SM, induced acute lung injury, ALI. Furthermore, we demonstrated that mere 146a5p delivered by HUC-MSCEVS targeted TIF-6 to negatively regulate inflammation in SM-induced ALI models in vitro and in vivo. Thus, HUC-MSCEVS treatment may be a promising clinical therapeutic after SM exposure.