In order to reduce the number of equipment regulation in the existing resistance calculation algorithm and realize the real-time online calculation of roadway resistance, firstly, according to the actual situation of mine ventilation system, the type of resistance alteration and its key characteristics are analyzed, and the feasibility of the design idea of resistance calculation algorithm based on resistance alteration is established. Secondly, a node pressure sensor placement algorithm based on the minimum vertex coverage theory is designed, and it is proved that the ventilation network can be divided into linear subnet and star subnet. Then, based on the ventilation subnet as the basic unit, combined with the real-time air volume of the roadway, a real-time online measurement resistance theory based on resistance alteration is proposed. Finally, taking the ventilation system in some areas of Sihe Coal Mine as an example, a simulation experiment was carried out. The results show that the proposed theory and algorithm can control the absolute value of the relative error of the resistance of a single roadway to about 5%, and the average absolute error of the resistance of all roadways is 0.1468%, which effectively reduces the number of equipment regulation and improves the real-time calculation of the resistance of the roadway.