Abstract: Natural fractures are encountered in the Luohe Formation within the Longdong tight oil area of Changqing Oilfield. Drilling with polymer drilling fluid is liable to lost circulation. As the formation is communicated with aquifer, with conventional plugging methods, the plugging material is dilution-prone and is washed by external fluid making it hard to stay in the thief zone, resulting in frequent lost circulations. To cope with this problem, a water-reactive plugging fluid was developed, by optimizing the prepolymer components and the addition of catalyst and diluent. In order to prevent it from being solidified through water reaction during injection, supporting injection tools with “packer + chemical storage chamber” were developed. Combining the plugging fluid and supporting injection tools, a loss circulation control technology for malignant water leakage layer in Longdong tight oil region was formed. The water-reactive plugging fluid had the characteristics of easy dispersion, self-emulsification, adjustable reaction rate, and high strength after consolidation, and the compressive strength of the consolidated sand body was greater than 5.6 MPa. The supporting injection tools safely pumped the water-reactive type plugging liquid to the leakage layer through a stepwise pressure increase. Loss circulation control technology for malignant water leakage layer was applied in thief zones in four wells in the Longdong tight oil area, which efficiently solved the lost circulation problem in Luohe Formation in one go. The field application show that the technology can solve the problem of leakage in the fractured formation when there is communication with the aquifer and provide technical support for the exploration and development of Longdong tight oil.