Objective To explore the effects of different levels positive end-expiratory pressure (PEEP) on patients with severe craniocerebral injury complicated with acute respiratory distress syndrome and its nursing measures. Methods A total of 46 cases of severe craniocerebral injury combined with acute respiratory distress syndrome patients in Xuzhou Central Hospital from August 2015 to August 2016 were selected. Changes of their arterial partial pressure of oxygen (PaO2), partial pressure of carbon dioxide in artery (PaCO2), oxygenation index (PaO2/FiO2), cerebral perfusion pressure (CPP), mean artery pressure (MAP) and intracranial pressure (ICP) were analyzed when PEEP changes from 3 cmH2O to 15 cmH2O. Appropriate nursing measures were taken during PEEP treatment. Results The value of PaO2was (73.4±9.8), (92.5±14.3), (105.0±16.9) and (114.6±16.4) mmHg when PEEP was 3, 7, 11 and 15 cmH2O respectively, and the difference was statistically significant (F=36.875,P<0.01). With the increase of PEEP, the value of PaO2, PaCO2and PaO2/FiO2showed tendency to ascend. There was a downward trend of MAP and CPP when PEEP was increased. With the increase of PEEP (3-11 cmH2O) ICP increased, and ICP was stable when PEEP was more than 11 cmH2O. Conclusions The safe range of PEEP is 3 to 15 cmH2O. Corresponding adjustment of PEEP according to patient individual condition, with proper nursing measures can improve therapeutic effects and reduce complications.