Abstract: Frequent casing failure incidents during drilling through the Carboniferous salt-gypsum formations in the platform-basin transitional area in the Tarim Basin have severely compromised drilling safety. To address the unclear mechanisms and lack of effective preventive measures for casing failure in this region, this study analyzed the characteristic patterns of typical casing failure cases based on drilling, logging, and mud logging data. Dominant factors for casing failure in salt-gypsum formations were identified, and a mechanical model was established for casing failures in such formations. This model was used to quantitatively assess the impact of parameters such as the lower suspended casing length, hole diameter enlargement rate, and casing centralization degree on casing safety factors. The research revealed that the casing failure mechanism in this area is the synergistic effect of hard mudstone pivot points, salt dissolution-induced hole enlargement, and eccentric loading, ultimately leading to casing buckling failure. Based on calculations from the mechanical model, three optimization measures were proposed: optimizing wellbore configuration by extending the intermediate casing setting depth of the second spud section to the lower boundary of the salt-gypsum formation and sealing the layer with large-diameter and high-strength casing; regulating drilling fluid properties to control salt rock dissolution rate, reduce hole diameter enlargement rate, and ensure wellbore regularity; and, performing reaming before running casing, and installing centralizers above the casing section sealing the salt formation to improve casing centralization degree. Field applications in four new wells demonstrated that implementing this technical solution reduced the casing failure incident rate to zero, significantly enhancing drilling safety and economic efficiency. The research findings provide crucial theoretical support and technical guidance for the safe drilling of deep salt-gypsum formations.