Taguchi's design of experiment and numerical simulation were applied in the optimization of an aluminum profile extrusion process. By means of HyperXtrude, the extrusion process was simulated and the effects of process parameters on the uniformity of metal flow and on the extrusion force were investigated with the signal to noise ratio and the analysis of variance. Through analysis, the optimum combination of process parameters for uniform flow velocity distribution was obtained, with the billet diameter of 170 mm, ram speed of 2.2 mm/s, die temperature of 465°C, billet preheated temperature of 480°C, and container temperature of 425°C. Compared with the initial process parameters, the velocity relative difference in the cross-section of extrudate was decreased from 2.81% to 1.39%. In the same way, the optimum process parameters for minimum required extrusion force were gained, with the billet diameter of 165 mm, ram speed of 0.4 mm/s, die temperature of 475°C, billet preheated temperature of 495°C, and container temperature of 445°C. A 24.7% decrease of required extrusion force with optimum process parameters was realized. Through the optimization analysis in this study, the extrusion performance has been greatly improved. Finally, the numerical results were validated by practical experiments, and the comparison showed that the optimization strategy developed in this work could provide the effective guidance for practical production.