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Management plans, actions and strategies for preventing and mitigating natural disasters require detailed information on natural and human-induced geohazards for the area under evaluation. Karst areas are particularly prone to instability due to the natural fragility of their environment but are also vulnerable due to human activity. In-depth studies of the factors controlling mass movement processes, including land use over time, become crucial for understanding instability mechanisms and future landscape evolution, as well as for designing preventive measures and control techniques. The Murge area, in the central part of Apulia (South Italy), is crossed by a vast network of dry valleys, locally named lame and gravine, whose morphology may resemble the most well-known canyons and gorges of the world. The genesis of these dry valleys is controversial and still the subject of continued debate, although their origin is directly related to the geostructural setting and the uplift of the Apulia foreland since the middle Pleistocene. Each of these karst valleys has particular morphometric characteristics as well as their own morpho-evolutionary history strongly linked to the different types of fault or fracture on which they developed. Also, geological and geotechnical characteristics of the rock substrate channel, and historic human-made slope excavation or remodeling play an important role. Unfortunately, several tragic events which occurred during the last decades have shown the susceptibility of the Apulian dry valleys to natural hazards, sometimes caused by human activities. This paper proposes, by means of a case study on a dry valley called Gravina di Petruscio in the Arco Ionico Tarantino subregion, a multidisciplinary approach using traditional methods of investigation and combining results to arrive at a critical appraisal of information that are suitable for a geohazard susceptibility analysis in karst environments. Geological, geostructural and geomechanical surveys, together with petrographic observations in thin sections of the outcropping materials, allow to understand the genesis of the valley and then its evolution mainly due to slope retreat processes. Both sides of the valley have been found to be affected by planar slides, wedge slides, direct toppling and falls, while the caves, mostly modified by humans, are affected by thinning, spalling and crushing of pillars, and partial or total collapse of cave roofs. The predisposing and triggering factors of the most common mass movements are presented and discussed. Mitigation and prevention measures for future planning, and remedial engineering structures are reported.