In the period of rapid development of civil aviation, ATC operation process is an important part. In order to study the key factors affecting ATC operation, a research model was constructed using DEMATEL-ISM method from four levels of personnel, equipment, environment and management, in order to determine the key factors of ATC operation. The results show that the influencing factors of ATC operation are divided into eight layers, among which, the stability of equipment, the working environment of equipment systems, the opening of the unit's sector, airport meteorological information, the ability to protect hazardous weather, and the input of safety management resources are the key factors, and the analysis results are combined to put forward suggestions and optimization measures, which can provide a reference for the development of ATC operation.