Drilling mud loss is of crucial importance in drilling. Lost circulation will extend the well construction period, cause investment losses, and even cause serious downhole accidents. In the Mizhi block of Changqing Oilfield targeted by this research, serious leakage occurred in many wellbore drilling processes, which has seriously affected the development of the block and caused economic losses. This paper focuses the mud loss during the drilling process of more than 200 wells in the Mizhi block, and counts the key loss data such as the lost horizons, the amount of lost drilling fluid, the average leak rate, and the density of the drilling fluid, and fully analyzes the possible reasons of the lost circulation. Collecting logging data, modeling geomechanics of some key wells and formations, taking cores and the geomechanical model is established. Analyzing the logging data and the specific leakage situation, the leakage mainly comes from fractured leakage, and the leakage horizon is mainly located at the bottom of the Liujiagou Formation, the entire interval of the Shiqianfeng Formation and the top of the Shihezi Formation. Most of the mud loss sections are sand-mudstone interbeds. Geomechanical analysis shows that the rock mechanical strength of the entire interval is difficult to support the stability of the wellbore under the drilling fluid density of 1.1 grams per cubic meter, but the block loss pressure is generally between 1.1 - 1.2 grams per cubic meter. Collapse and leakage coexist in the wellbore. This study gives the method of drilling fluid optimization, and gives the possible reasons for the leakage from the perspective of geomechanics, which has important guiding significance for the further development of the Mizhi block.