Abstract: This study aims to establish the design space of the key processes for drop-on-powder 3D printing based on design of experiment (DoE). By utilizing Minitab, an experimental scheme with three factors, two levels and three center points was designed to analyze the factors that significantly affected the tablet quality attributes. Furthermore, the factor interactions were analyzed using Minitab. subsequently, the computer aided drafting (CAD) software was used to adjust the model volume with fixed radius/height ratio (r/h=1.25) and establish a linear regression equation between model volume and dose. As a result, the drug dose could be controlled in a flexible manner. The finally determined process parameters were:ink-jet level is 12, layer thickness is 150 μm, and the X-axis printing head speed of 635 mm·s^-1. Regression equation between drug content (y) and model volume (x) was y=0.062 x-0.582 7 (R²=0.999 9) showing good linear relationship. This indicated that robust and feasible process parameters were obtained through DoE, and the preparation of personalized-dose tablets was realized with good reproducibility.