This article investigates the seismic response of a tailings sand material in the context of site response analysis. The computed response is contrasted with that obtained for an equivalent deposit consisting of a well-characterised natural sand. Initially, the fundamental properties of both materials are used to interpret and compare their behaviour in the framework of Critical State Soil Mechanics (CSSM). Subsequently, both materials' monotonic and cyclic responses are calibrated for an advanced bounding surface plasticity model. Finally, the impact of different calibration approaches is examined through site response analyses under a strong motion. This process identifies fundamental differences between the two geo-materials, impacting the single elements simulations, especially the accuracy of undrained cyclic triaxial tests. The site response analyses examined herein show the impact of the calibrations adopted for both materials in terms of acceleration response spectra, displacements, and excess of pore water pressures (PWP). Although a relatively deep phreatic surface is adopted, the cyclic resistance and permeability of both materials plays a dominant role in the site response characteristics, controlling the excess PWP generation and hence the non-linear behaviour in the soil deposit. Finally, parametric studies are also conducted to explore the impact of permeability of the sands in the site response.