An electrostatic discharge (ESD) protection device and an operation method of the ESD protection device are provided. The ESD protection device includes an ESD current rail, an ESD protection element string, and a bias circuit. A first end and a second end of the ESD protection element string are electrically connected to the ESD current rail and a signal pad, respectively. The ESD protection element string includes a first ESD protection element and a second ESD protection element that are serially connected. The bias circuit is electrically connected to the ESD protection element string to provide a bias voltage to a common connection node between the first ESD protection element and the second ESD protection element.