Abstract: The Tertiary mudstone in the northern margin of Qaidam basin is the main regional caprock of oil and gas, characterized by lateral distribution stability and strong sealing ability. According to drilling, logging and breakthrough pressure data, the macroscopic development characteristics and microscopic sealing mechanism of the Tertiary mudstone caprock in Lenghu area of northern Qaidam basin were studied. Furthermore, the mudstone thickness, diagenetic stage, breakthrough pressure, overpressure coefficient and brittleness index are selected as evaluation parameters to quantitatively evaluate the sealing capacity of mudstone caprock. The results show that there is a series of mudstone caprock developed, such as Lulehe, Xiaganchaigou and Shangganchaigou Formations. Mudstone caprock diagenesis is in the early diagenetic stage A to the middle diagenetic stage B. The breakthrough pressure of mudstone caprock reaches 1.1 MPa, which has the ability of sealing commercial oil flow, and reaches 2 MPa, which has the ability to seal commercial gas flow. In general, the sealing ability of the upper member of Xiaganchaigou Formation and Lulehe Formation caprock is the best and the lower member of Xiaganchaigou Formation is relatively weak. The sealing ability of Shangganchaigou Formation is the worst. The results of sealing evaluation match with the exploration practice.