Abstract: The flow and mixing performance of fluid in T-shaped micromixer with non-aligned inputs are investigated numerically by using a three-dimensional numerical simulation method. The analysis results show that the displacement differences appear in the direction of gravity due to the arrangement of non- aligned inputs. After fluid flowing into the channels, the fluid contact areas increase. The apparent spiral flows are generated along the axial direction of the channel, thus further strengthening mixing performance. Meanwhile, this paper presents a numerical design methodology for different geometrical configurations, which systematically integrates computational fluid dynamics (CFD) with an optimization methodology based on the use of Taguchi method. The geometric features of this micromixer geometry have been optimized based on the change of signal-to-noise ratio. The influence degree of parameters on mixing effectiveness is: width of the inlet channel w > height ratio of inlet and main channels h/H > inflow angle of the inlet channel α.