The influence of interior non-coherence of leading generator cluster to the transient stability dominant mode is studied to deal with the complex transient instability under the background of interregional interconnection of power grid. Based on the equivalent system model and EEAC theory, the influence factors of interior non-coherence of leading generator cluster to transient stability of dominant mode is deduced when the system has the chain structure, the influence rules of each influence factor is given qualitatively, and simulation example of simple system and real power grid is studied lastly. The theoretical and simulation results show that expansion of interior non-coherence of leading generator cluster has an adverse impact on system transient stability, and this impact is associated with structure parameter, operation mode of power grid, and the inertia distribution of leading generator cluster which has the characteristic of interior non-coherence.