The high-speed fluid–structure interaction (FSI) occurring between a skin panel and a turbulent shock-boundary layer interaction (SBLI) are investigated with large eddy simulations (LES). The SBLI is comprised of a Mach 4 and unit Reynolds number of 2.375×107 (/m) flow interacting with an oblique shock of strength p3/p1≈8.5 and angle σ≈30deg. The inviscid point of impingement on the flexible panel occurs near the mid-chord length. The fully clamped rectangular panel has the aspect ratio and non-dimensional panel thickness of b/a=1.377 and h/a=0.003, respectively. The strong SBLI induces a large flow separation of length Lsep≈0.7a (or equivalently ≈23δin) with a wide range of turbulent scales, including the characteristic low-frequency unsteadiness. Fluid and structural responses are compared across different classes of interaction, namely: rigid surface; one-way application of SBLI loads to the structure; and two-way interaction between the flow and structure. The interplay between the SBLI and flexible panel is elucidated using detailed analysis that includes proper orthogonal decomposition (POD), dynamic mode decomposition (DMD), and the recently developed Lagrangian modal analysis (LMA) for the deforming meshes. The large panel deflections (∼1h) result in structural non-linearity associated with the coupling between bending and stretching of the panel, manifested in terms of increased modal frequencies of the panel deflection.