A mechanical multi-frame RF/infrared composite interference semi-physical simulation system includes a microwave anechoic chamber, a three-axle table, a table control system, a RF interference simulator, an infrared interference simulator, a mechanical multi-frame moving system, a servo system, and an integral real-time simulation control system. The three-axle table, the table control system, the RF interference simulator, the infrared interference simulator, and the mechanical multi-frame moving system are arranged inside the microwave anechoic chamber, and the integral real-time simulation control system is arranged outside the microwave anechoic chamber. The RF interference simulator and the infrared interference simulator are mounted on a moving platform of the mechanical multi-frame moving system. The integral real-time simulation control system is composed of a multi-node real-time computer network including a master control computer, an acquisition computer, a RF interference control system, an infrared interference control system, a real-time communication network, a simulative master control system and a monitoring system. The real-time communication network is built up by the utilization of reflective memory networking, and information transmission and real-time control among devices of the simulation system are realized.