To enhance the understanding of safety of multi-chamber mixing processes, a multiphase flow CFD numerical model based on the Eulerian method was established for the continuous mixing of multi-component materials in a multi-chamber kneader, taking a cast polymer bonded explosive (PBX) as the object. Experimental verification was conducted to confirm the reliability of the model. Based on the model, the influence laws of key process and structural parameters including blade rotation speed, kneading clearance and blade profile on the mixing safety stimulus were studied. The results show that the pressure level gradually decreased from the feeding chamber to the discharging chamber. Increasing the blade rotation speed was beneficial for reducing the pressure in the chambers, but the shear stimulus significantly increased. As the blade rotation speed increased from 15 r·min-1 to 75 r·min-1, the peak pressure in the kneader decreased from 402966 Pa to 258107 Pa, and the peak shear stress increased from 6268.5 Pa to 16607.9 Pa. Increasing the kneading clearance significantly reduced the pressure and shear stress in the chambers. As the kneading clearance increased from 1 mm to 5 mm, the peak pressure in the kneader decreased from 391094 Pa to 284478 Pa, and the peak shear stress decreases from 8320.5 Pa to 3982.6 Pa. Compared with the two-wing-two-wing blades, four-wing-two-wing blades produced stronger shear stimuli due to more kneading sites, but the blade profile had a smaller impact on the kneading pressure. When the four-wing-two-wing blades and two-wing-two-wing blades were used in chambers 1-7, the peak shear stresses in the kneader were 7481.3 Pa and 4518.1 Pa, respectively.