Abstract: Frequent severe lost circulation occurs during Mesozoic drilling in Zhengning Oilfield, while the loss mechanism remains unclear and efficient plugging of loss zones fails to be achieved, which seriously restricts the exploration and development of tight oil and gas reservoirs in this block. To address this issue, the mineral composition and microstructure of the loss intervals were analyzed by X-ray diffraction and scanning electron microscopy. The results show that the content of easily hydrated minerals in the loss intervals is low and the overall dispersion capacity of the rocks is weak, while the hydration dispersion is significantly enhanced in local intervals with high illite/smectite mixed-layer content, and drilling fluid invasion may induce deterioration of the rock structure. Natural fractures are identified as dominant controlling factor for lost circulation. On this basis, an innovative fracture-width inversion method based on drilling fluid properties and loss data is proposed, and a fracture-width calculation chart under different drilling fluid viscosities is established, enabling rapid quantitative evaluation of fracture width in the loss intervals. Using this chart, 75 groups of historical lost-circulation data were inverted. The results indicate that natural fractures expand significantly under drilling-fluid pressure during loss events, and large fractures wider than 4 mm account for more than 55%, reaching the level of hydraulic fractures. According to the fracture dimension distribution, six different types of lost-circulation additives were systematically evaluated and optimized, and a lost circulation additives design chart corresponding to different fracture widths is established. Field applications show that this method remarkably improves the response and plugging efficiency for lost circulation. For 7 wells treated under the guidance of this chart, the success ratio of first-attempt plugging increased by 65.7% and the average operation time was reduced by 83.6% compared with conventional plugging practices, providing strong technical support for the safe and efficient development of tight oil and gas resources in Zhengning Oilfield.