The cross tunnel-slope system has a strong sensitivity to seismic waves and is extremely prone to potential seismic damage. To investigate the seismic failure mechanism and interaction of the cross tunnel-slope, the cross tunnel-slope model is constructed and tested by shaking table tests. The dynamic strain of the tunnel and acceleration response of the slope are analyzed. Furthermore, the failure process and dynamic response of the model are discussed in detail by the Hilbert Huang transform (HHT) and the seismic damage phenomenon. The dynamic response of the upper-span tunnel is significantly stronger than that of the under-pass tunnel. The cross tunnel changes the stress distribution of the slope and has a significant amplification effect on the seismic response of the slope. Additionally, it is found that variation trends of the marginal spectrum obtained by the HHT can reflect damage processes of the model. The high-frequency components (6–10 Hz) mainly induce the local deformation of the slope. The dynamic failure mode of the slope with the cross tunnel is tension cracks - shear failure - sliding. Meanwhile, the tunnel structure will be subject to seismic inertia forces and landslide thrust in the process of the slope deformation and instability. The upper-span tunnel is dominated by longitudinal bending and overall displacement to the free surface of the slope, with partial position lifting and staggering. However, the under-pass tunnel under the slope in the line axial direction can be used as a beam-type structure to bear a certain landslide thrust.