We used a novel viral- and bacterial-simulation-induced ALI model to prove the protective effects of ibrutinib on ALI, which are attributed to regulation of the BTK-, FLT3-, and EGFR-related signaling pathways, inhibition of the expression of downstream inflammatory factors (NFκB, IL-1β, IL-6, TNF-α, and IFN-γ), and improvement of neutrophil, as well as lymphocyte, aggregation. Here, EGFR is linked to acute respiratory distress syndrome.