The occurrence of moderate to severe acute respiratory distress syndrome due to traumatic brain injury is not uncommon and is associated with an extremely high incidence of morbidity and mortality. Owing to the complex interaction between the lung and brain, protective ventilation for the lung with lower tidal volume and higher positive end-expiratory pressure with or without mild hypercapnia might be harmful for the brain, and maintaining normocapnia or mild hypocapnia by increasing tidal volume or respiratory rate (or both) with lower positive end-expiratory pressure levels for protecting the brain might lead to ventilator-induced lung injury. Balancing the end-point between lungs and brain becomes a challenging issue, and non-conventional modes of mechanical ventilation might play a role in the more difficult clinical cases. In this commentary, the authors discuss the rationale, based on the physiologic principle of targeting both vital organs, of applying high-frequency oscillation and tracheal gas insufflation in acute respiratory distress syndrome patients with traumatic brain injury.