In order to ensure the steady increase of oil and gas equivalent, the drilling area is expanding year by year, and the problem of lost circulation is becoming increasingly prominent, which has seriously restricted the drilling speed and efficiency. Efficient treatment means have been formed for plugging a single lost circulation layer, but there is no effective means to control multiple sets of lost circulation layers in long open hole well sections. Therefore, this paper analyzes the lost circulation layers in Changqing Oilfield, and clarifies the lost circulation mechanism of the lost circulation layers. After the occurrence of leakage, the “multi parameter” leak detection tools, mainly including well temperature method and flow method, are used to identify the leakage horizon of the long open hole section, determine the location of the leakage, and finally the developed efficient hydrophobic plugging working fluid is used for special plugging, forming a set of long open hole multi-layer system precise plugging technology in Changqing Oilfield. The leakage layer identification accuracy of the multi parameter leakage detection tool is ± 30 m, and the leakage detection time is 4-6 h, providing data support for subsequent plugging. The high-efficiency drainage and plugging working fluid is composed of cementitious materials and inert materials. The pressure bearing capacity of 2 mm joint plate can reach 12 MPa, meeting the requirements of high pressure sealing. The technology was applied to three wells on site, and all of them were successful in plugging at one time, providing technical references for plugging encountered in drilling and exploration of unconventional oil and gas wells in China, and helping to increase drilling speed and efficiency.