During the investigation and evaluation of Uranium deposits in Shiquantan area of Qaidam Basin，the formation pressure anomaly was encountered. The formation pressure coefficient of 0~600m is 1.25~1.4. The formation is easily soluble with a high salt content of up to 1.025%. Accidents such as stuck and collapse usually happened during the drlling process as drilling information about this area is less. In this paper， a set of anti-salt and anti-collapse flushing fluid system suitable for the strata in this area is proposed by analyzing the lithological characteristics of the strata in this area， and preferentially selecting the corresponding slurry-making clay and treatment agent for the flushing fluid. As a result， this systerm has good anti-salt and anti-collapse performance， mainly showing as follows： the apparent viscosity 38MPa·s， the dynamic shear force is 16.4Pa， the API filter vector is 4~5mL， the mud skin is thin and dense with the thickness of 0.3~0.4mm which has good wall protection effect. It effectively solved the problems such as shrinkage in salt-gypsum layers， hole collapse and destabilization of flushing fluid under abnormal conditions of high pressure in this area. As a result， the average monthly efficiency is increased from 729.76m to 1378.78m， the hole expansion rate is reduced from 130% to 19.4%， and the cost of mud material and water is reduced from 57.91RMB/m to 38.92RMB/m. Good economic benefits have been achieved in practical application in the field which make it has the value of popularization and application.