This study focuses on the filter cartridge of radioactive iodine protective mask. By combining computational fluid dynamics numerical simulations with experimental methods, a mathematical model of airflow within the filter cartridge was established to analyze the flow field and pressure drop distribution. The advantages and limitations of three common filter cartridge structural designs were evaluated, and the relationships between airflow rate, activated carbon particle size, and pressure drop were investigated. Furthermore, the effects of airflow rate, temperature, and humidity on the removal efficiency of methyl iodide were examined. The results indicate the following: (1) The fan-shaped filter cartridge exhibits uniform flow distribution, high activated carbon utilization, and low pressure drop, with a deviation between simulated and experimental values within 8%, confirming the reliability of the mathematical model. (2) Activated carbon particle size significantly influences pressure drop; when the average particle size is ≤0.4 mm, the pressure drop increases substantially, making it unsuitable for filter cartridges. (3) When the airflow rate exceeds 220 L/min, the methyl iodide removal efficiency begins to decline significantly, falling below the standard threshold of 99% at 260 L/min. (4) Environmental impact studies reveal that the removal efficiency remains stable within a temperature range of 10°C to 60°C but decreases notably when relative humidity exceeds 50%, dropping below 99% at 95% humidity. Under normal conditions, the filter cartridge maintains a methyl iodide removal efficiency of over 99%. This research provides important theoretical insights and technical support for the development of radioactive iodine protective mask filter cartridges.