A series of computational studies were performed to investigate the biomechanical responses of the pig head under a specific shock tube environment. A finite element model of the head of a 50-kg Yorkshire pig was developed with sufficient details, based on the Lagrangian formulation, and a shock tube model was developed using the multimaterial arbitrary Lagrangian-Eulerian (MMALE) approach. These two models were integrated and a fluid/solid coupling algorithm was used to simulate the interaction of the shock wave with the pig's head. The finite element model-predicted incident and intracranial pressure traces were in reasonable agreement with those obtained experimentally. Using the verified numerical model of the shock tube and pig head, further investigations were carried out to study the spatial and temporal distributions of pressure, shear stress, and principal strain within the head. Pressure enhancement was found in the skull, which is believed to be caused by shock wave reflection at the interface of the materials with distinct wave impedances. Brain tissue has a shock attenuation effect and larger pressures were observed in the frontal and occipital regions, suggesting a greater possibility of coup and contrecoup contusion. Shear stresses in the brain and deflection in the skull remained at a low level. Higher principal strains were observed in the brain near the foramen magnum, suggesting that there is a greater chance of cellular or vascular injuries in the brainstem region.