The evaluation of a new method based on the integration of geochemical, morphological, and structural analyses for the study of neotectonics in clay basins is presented. More than 900 helium soil-gas samples were collected over an area located in the central sector of the Adriatic foredeep (central Italy). Soil-gas distribution has been compared with the location and orientation of the main structural features described in the literature and/or characterized by field surveys and morphotectonic features obtained by air-photo interpretation and drainage network analysis. Collected data were statistically analyzed and compared by means of rose diagram plots. A geostatistical approach was used to describe the spatial behavior of the helium distribution. The comparison of the morphological and structural elements with the observed geochemical anomalies shows that the northwest-southeast is the most representative direction in agreement with the known Apennine structural trends. Moreover, the presence of north-south and east-west trends in the helium regional distribution, observed in the central and southern sectors of the studied area, is thought to be caused by a more recent deformation phase acting along these directions. This hypothesis is strengthened by the good correspondence, both at regional and local scales, between geochemical data and the results of the structural and geomorphological analyses. Furthermore, the magnitude and the anisotropic distribution of the helium anomalies in the residual maps indicate that at local scale, this gas could be related with the distribution of the hydrocarbon reservoirs occurring in the area.