The present disclosure relates to a system and method for operating a main brake in case of a failure of an autonomous driving function of an autonomous vehicle. the system for operating the main brake in case of a failure of the autonomous driving function of the autonomous vehicle includes an autonomous driving control unit configured to perform control such that the autonomous vehicle travels in the autonomous driving mode, a main brake control unit configured to perform first communication with the autonomous driving control unit and to output a first control signal so that a frictional braking force is generated to a main brake by hydraulic pressure, and a regenerative braking control unit configured to perform second communication with the main brake control unit and to output a second control signal so that a regenerative braking force is generated to a motor.