In order to realize the sustainable development of the field of automotive industrial engineering and reduce the emissions of heavy-duty trucks (HDTs), a simulation analysis method that combined fluid–structure coupling and a discrete phase model was proposed in this study. The pressure, velocity, and other parameters of an HDT air filter and its cartridge were analyzed by using CFX and the Static Structure module in the ANSYS software. The results showed that under six different flow rates, the error between the simulation results and the test results was basically less than 3% (the maximum error was 3.4%), and the pressure distribution of the fluid in the air filter was very uneven, leading to a severe deformation of 3.51 mm in the filter element. In order to reduce the pressure drop of the air filter and the deformation of the filter element, the position of the air inlet duct, the height of the filter element, and the number of folds of the air filter were optimized in this study. The optimization results showed that when the rated flow was 840 m3/h, compared with the original structure, the pressure drop of the air filter was reduced by 445 Pa, the maximum deformation of the filter element was reduced by 54.1% and the average deformation is reduced by 39.8%. After the optimization, the structural parameters of the air filter were as follows: the position of the air inlet moved down 126 mm along the shell, the filter height was 267 mm, and the pleat number of the filter element was 70. The simulation method and optimization design method of an air filter based on fluid–structure interaction presented in this study can be used to reduce the pressure drop, improve the engine performance, and reduce the amount of harmful emissions.