The Equations of motion of mega-sub control system is established in this paper when the sub-structure is modeled as multi-degree of freedom system. The transfer function of the system is then derived by using the complex modal theory. The ultimate state function is obtained by using the response surface method and then on the basis of the first passage mechanism of random vibration, the calculation method of dynamic reliability of the system is analyzed. Finally, the reliability sensitivity of the random parameters of the structure to story drift angle is analyzed when the ground motion is considered as random excitation and the structure is considered in elastic state. Results indicate that the mean stiffness of substructure has poor sensitivity to story drift angle, while the sensitivity of the mean stiffness of main structure and damping ratio of isolation layer to story drift angle is strong.