There has been a great controversy over the setting of the cross passage in a large diameter highway tunnel and how to set up, while the mechanical behavior of the cross passage structure is of great significance for evaluating and controlling its risk. In order to explore the mechanical behavior of cross passage deformation joint under the influence of uneven deformation and seismic performance and determine the best setting position, the design scheme of Qianjiang River Tunnel project is taken as a basic calculation model for the analysis. Based on the characteristics of Qianjiang River Tunnel engineering geological environment, four relative deformation models are proposed; artificial site seismic wave of Qianjiang River are established; finite element analysis model is built to study the mechanical behavior of the tunnel and the cross passage respectively from two aspects of inhomogeneous deformation and aseismatic performance. Based on analysis, the optimal setting location and allowable deformation of cross passage deformation joint are determined. It is concluded that integrated taking into account the effects of inhomogeneous deformation and aseismatic behavior, the optimal setting location of deformation joint of cross passage of Qianjiang River Tunnel is 1.2 m away from the edges of tunnel; and the optimal allowable deformation is greater than or equal to 6 cm.