Damage to buried pipes under seismic landslide actions has been reported in many post-earthquake reconnaissance. The landslide-pipe problem in the technical literature has been often investigated using simplified analytical methods. However, the analytical methods ignore the real mechanism of pipe response under natural dynamic slope instability. The dynamic slope instability is significantly influenced by its lateral boundary interface (LBI) characteristics. In this study, slope-pipe interaction (SPI) under seismic loading, focusing on the effect of LBI properties, is evaluated by continuum numerical simulation using the SANISAND constitutive model in FLAC3D. The results show that the geometry of the failure mass varies from 2D to 3D by increasing the stiffness at the slope boundaries (from smooth to hard) and the maximum pipe deformation decreases by around 40%. Moreover, the response components of maximum axial stress, bending moment, and shear stress of the pipe occur at the end sections of the buried pipe and near the boundaries of the landslide zone. However, the maximum pipe deflection occurs in the middle section of the pipe. The results of shear force-shear displacement curves demonstrate that the soil-pipe interaction stiffness is variable along the pipe length and can be estimated by a hyperbolic equation.