Large defect-free domains of a hexagonal packed monolayer of silica spheres with the size of 4000 µm2 were successfully prepared by dual-speed spin coating. Experimental design and statistical analysis instead of the traditional ‘changing one separate factor at a time’ (COST) approach were employed to guide the implementation of the experiments. With its assistance, the hexagonal-close-packed (HCP) percentage was elevated to 84% in this study. Furthermore, almost all the samples with parameters in the selected ranges possessed more than a 60% HCP percentage. In addition, the optimal values for parameters of the suspension concentration, the first rotation speed, and the spinning time to obtain well-ordered silica spheres arrays were also identified as 30 wt.%, 1000 rpm and 20 s, respectively.