Background The method for estimating the resistance in airway (R) and compliance in lung (C) is one of critical technologies in developing the individualized and precise ventilation. Objective In application of positive airway pressure ventilation, a method was proposed aiming at conducting the method to online estimate the R and C. Method With a negative pulse pressure superposed upon the expiratory positive airway pressure (EPAP), a discharged airflow in the airway was produced, and the R and C were calculated with the discharged airflow. And then, taking the simulated normal adult, typical patients in COPD and in ARDS as the experimental subjects, designing a simulated platform, the simulation experiments were carried out to calculate R and C. Results The errors in the results of R and C respectively are 3.398% and -3.288% for normal adult, 1.265% and -1.348% for patient in COPD, 3.400% and -3.286% for the patient in ARDS. Conclusions The experiments suggested that the method with a negative pulse pressure superposed upon the EPAP to conduct the R and C is well practicable. The investigating in the method will be beneficial for further studying the intelligent and precision ventilation.