Abstract: With the information computing, network communication, and data processing capabilities developing rapidly, human social life has a great changes. However, due to the openness and sharing of wireless network, cyber-physical system is vulnerable to all kinds types of network attacks. As one of the most common attack methods used by malicious attackers in cyber-physical system, denial of service (DoS) attacks have received widespread attention and in-depth research. In this regard, this paper considers a malicious attacker launching a DoS interference attack on the cyber-physical system with inherent random packet loss in the wireless transmission channel between the sensor and the estimator, and proposes an attack detection based on the combination of the optimal state estimation system and the fault detector. Finally, the effectiveness of the proposed detection model is verified by a numerical simulation example of MATLAB.