An over-voltage protection circuit includes an over-voltage detection circuit, a voltage generator and a switch for providing over-voltage protection between two pins of a USB Type-C port. The over-voltage detection circuit provides an over-voltage signal according to the level of the second pin. The switch includes a first end coupled to the first pin, a second end coupled to the second pin and a control end coupled to a control signal. When the over-voltage signal does not indicate an over-voltage occurrence at the second pin, the voltage generator provides the control signal having a first level for operating the switch in a first region. When the over-voltage signal indicates an over-voltage occurrence at the second pin, the voltage generator adjusts the control signal to a second level for cutting off the switch. The switch operates in a second region after the over-voltage occurrence and before the switch is cut off.