Both the high-speed railway and air transportation network are the backbone of the interregional transport network and cover important cities in a country. Taking cities as nodes, a comprehensive interregional transportation network consisting of high-speed railways and civil aviation can be constructed. This network undertakes a huge passenger transportation task, so the failure of this network will cause serious economic losses and even casualties. In the Air-High-Speed Railway Transportation Network (A-HSRTN), the two transport modes can operate independently and can be alternatives. The analysis of the A-HSRTN helps planners to have a more comprehensive understanding of the vulnerability of the interregional passenger transport system. Mechanical failure, extreme weather and even man-made sabotage can threaten the operation of airports and stations. Optimizing the deployment of prevention resources can avoid or reduce the loss caused by those failure events in the A-HSRTN. This paper establishes a tri-level model to optimize the deployment of prevention resource from the perspective of predisruption response. This model takes the high-speed railway and air transportation system as an integrated transportation network to assign the limited prevention resources. The model aims to minimize the travel demand that cannot be satisfied in the worst failure scenario. Taking the A-HSRTN in mainland China as an example, this paper analyzes the model performance and the defense strategy obtained by this model. These case studies demonstrate that the method and model proposed in this paper can mitigate the vulnerability of the A-HSRTN.