In order to improve the treatment of patients with ventilator-associated pneumonia (VAP) in severe traumatic brain injury (TBI) and to effectively suppress the inflammatory response and enhance blood oxygen indicators, we conducted an innovative bronchoalveolar lavage (BAL) treatment using N-acetylcysteine (NAC). To conduct this study, we divided patients with VAP in severe TBI into a control (CTRL) group and a BAL group. The control group received BAL with saline, while the BAL group received BAL with NAC in addition to standard care. We compared the clinical treatment, degree of inflammation, blood oxygen index, and safety of both groups pre- and post-BAL. The results showed that BAL with NAC was more effective in reducing the duration of antibiotic use, imaging uptake, fever reduction, mechanical ventilation, and ICU stay, as well as CPIS and APACHE II scores. Moreover, the BAL group demonstrated greater improvement in ventilation, as indicated by increased values of PaO2, SaO2, and OI, and a more substantial decrease in PaCO2. Furthermore, BAL treatment effectively suppressed the level of inflammatory response in the body and more significantly reduced TNF-α, CPR, PCT and MIP-1α levels. Adjuvant treatment with BAL effectively improved clinical outcomes and reduced mortality in severe TBI patients with VAP, while maintaining a high level of safety during the BAL operation. Therefore, BAL using NAC holds significant potential in the salvage of patients with severe TBI combined with VAP.