The EMI filter of infrared cryocooler driving system was designed and simulated. With considering the characteristic of the crucial device in system, the co-simulation model of the system was built by using the appropriate algorithm. The interference mechanism was extracted and analyzed with the assist of the co-simulation model. Based on the impedance mismatch theory, the relationship of the filter performance and the impedance of the source and load was analyzed. Finally, based on interference mechanism, a method for filter design and optimization was raised, and it can optimize the filter’s performance and reduce redundancy effectively. A test was established and proved the feasibility and accuracy of the method.