Abstract: The severe leakoff in the Palaeogene composite salt layer of the Kuqa piedmont zone, the Tarim Basin, brings about tremendous challenges to drilling safety. The geological and geomechanical characteristics of key thief zones of the Kuqa piedmont composite salt layers were investigated. Moreover, in accordance with drilling operation parameters, the leak-off types were identified, the leakoff-prone lithologic association and leakoff pressure were analyzed, and the leakoff prevention method was developed. The research showed that the gypsum-salt rock with interbeds of salt-bearing and gypsum-bearing mudstone, and gypseous mudstone with interbeds of mudstone and limy mudstone are the main leakoff lithologic associations. The macro- and micro- scale analyses indicated no material basis for direct leakoff-natural fractures are underdeveloped, and the measured porosity and permeability are low. The tensile strengths of gypsum-bearing and salt-bearing mudstone are 0.61−1.12 MPa, averaging 0.946 MPa, and such layers are prone to fracturing via pressurization. The average leakoff rate of drilling fluids is less than 20 m³/h and represents minor-small leakoff, which can be effectively mitigated by reducing pump rates and mud density. The analysis of geology, geomechanics and engineering characteristics of inter-salt thief zones demonstrated that the leakoff of composite salt layers is attributed to induced fracturing, and the leakoff pressure is equal to the formation fracturing pressure (close to the minimum horizontal principal stress), which is validated via the comparison between the simulated stress field and the leakoff points during drilling. Given the above-mentioned, the key to preventing leakoff of composite salt layers is to clarify the leakoff-prone lithologic association of gypsum-salt rocks and calculate the minimum horizontal principal stress from the viscoelastic three-dimensional geomechanical model of composite salt layers. The findings of this research are of great significance for reducing inter-salt leakoff.