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During the oil shale drilling in Group Q of Block GL, the shale is prone to hydration, deterioration, sidewall exfoliation and frequent collapse, which affects the efficient exploration and development of shale oil. In order to reveal the mechanism of wellbore instability in the shale formation, the tectonic characteristics of shale are studied by combining microscopic and macroscopic methods, which identifies three key factors of physics, chemistry and mechanics about wellbore instability. Based on the analysis of earth stress and rock mechanics parameters, the experiment has established the prediction model of “fluid-solid-chemical coupling” collapse pressure of shale formation in Group Q, and calculated the safe drilling fluid density window for the horizontal wells of shale oil in Block GL by the prediction model. The main factors of wellbore instability in shale formation, deterioration characteristics and high density of oil-based drilling fluid on the well site is combined. The targeted plugging anti-sloughing and strong wetting agent were developed by using laser particle size instruments and pressure transmission experiments. A high thixotropy and strong plugging oil-based drilling fluid system is formed. The research results have been successfully applied in 16 horizontal wells of the shale oil test platform. The excellent rheological property, reliable plugging and bearing capacity and outstanding wellbore stabilization effect provides technical support for high-quality and efficient exploration and development of shale oil in Block GL. The “fluid-solid-chemical coupling” wellbore stabilization technology of continental shale oil formed in this study can provide a reference for the exploration and development of similar types of shale oil and gas reservoirs.