This paper illustrates the results of the numerical modeling carried out to investigate the local seismic response in the Southern part of the city centre of L'Aquila (Italy), namely in the area of Via XX Settembre, harshly damaged by the April 6, 2009 earthquake. The upper portion of the subsoil in this area is irregularly affected by peculiar local conditions that may have originated major amplification of the ground motion during the main shock. The geotechnical model of the subsoil and related parameters, defined based on accurate site investigations, were used for a seismic response analysis. The results of this analysis indicated that the site effects due to local subsoil conditions played an important role in the observed damage distribution.