In the drilling process in salt soluble formation of Qinghai, the upper shale water swelling with borehole shrinkage, the lower potasium salt mineral layer corrosion lead salt intrusion and borehole diameter expanding; gravel clastic rock with poor cementation, collapsing and block falling, according to these construction difficulties, the study was carried out on the brine mud adaptability to lithology. By orthogonal experiment method in the laboratory and practical preparation in the field, 4 groups of brine mud formulas were optimized. Compared with the ordinary low solid mud in the application, the average penetration rate increased from 1.015m/h to 1.195m/h, borehole diameter expansion rate decreased from 7.83% to 4.36%, hole backreaming loss decreased from 3.05% to 1.41%, the mud cost decreased from 731.3 yuan /m3 to 503.8 yuan/m3.