A hardware Trojan immunity device and an operation method thereof are provided. The hardware Trojan immunity device is disposed in a data transmission path between an output terminal of a first circuit and an input terminal of a second circuit. The hardware Trojan immunity device includes a multiplexer, an arbitrary pattern generator (APG) and a monitoring circuit. A first input terminal of the multiplexer is coupled to the output terminal of the first circuit. An output terminal of the multiplexer is coupled to the input terminal of the second circuit. The APG is coupled to a second input terminal of the multiplexer to provide pseudo-random data. The monitoring circuit is coupled to a control terminal of the multiplexer. The monitoring circuit is configured to monitor a data activity of the data transmission path and to control a routing of the multiplexer according to the data activity.