San Gimignano, the 'City of the Beautiful Towers' is located on the top of a hill in 'Val d'Elsa', about 60 km south of Florence (Italy). It was founded by the Etruscans in the 3rd century BC and in the Middle Ages it was a relay point along the Via Francigena for pilgrims on their way to Rome. From 1199 to 1353 AC the city saw its period of greatest splendour. As symbols of the wealth and power of the strongest major families, seventy-two tower houses were built in that period. Fourteen of these have survived to now and they represent a priceless heritage. Because of their significance, an important multi-disciplinary research project (named RiSEM) has been founded by the Regional Government with the aim of developing new investigation techniques for seismic risk assessment of monumental buildings. The present paper provides a synthetic report of the main aspects concerning the definition of the geotechnical model and the seismic soil-structure interaction analyses performed. The first part of the report, after some brief historical notes, describes the site conditions, including morphological, stratigraphic and geotechnical subsoil characterization from a recent survey. The results of the geotechnical investigations (two boreholes with taking of undisturbed samples, down hole and laboratory tests, both in static and dynamic conditions) are presented and discussed. In the second part, a general overview of the soil-structure system and a description of the main features of its components are given. The local seismic response analyses of the site and the soil-structure FEM analyses performed on the "Torre Grossa" using the computer program SASSI2000 (Lysmer et al., 1999) are also described. Real strong motion recordings were selected according to the local seismic hazard and used in the analyses. The numerical modelling results obtained both in time and frequency domain are presented and discussed in the paper.