The Kenics static mixer is one of the most widely studied static mixers, whose structure–function relationship has been studied by varying its aspect ratio and modifying the surface. However, the effect of the symmetric structure of the Kenics static mixer itself on twisting the fluid has been neglected. In order to study how the symmetrical structure of the Kenics static mixer impacts the fluid flow, we changed the center position of elements at twist angle 90° and introduced the eccentricity factor γ. We applied LHS-PLS to study this non-standard Kenics static mixer and obtained the statistical correlations of the aspect ratio, Reynolds number, and eccentricity factor on relative Nusselt number and relative friction factor. We analyzed the results by comparing the PLS model with the univariate analysis, and it was found that the underlying logic of the Kenics static mixer with an asymmetric structure became different. In addition, a non-standard Kenics static mixer with an asymmetric structure was investigated using vortex generation and dissipation through fluid flow simulation. The results demonstrated that the classical symmetric structure has a minor pressure drop, but the backward eccentric one has a higher thermal-hydraulic performance factor. It was found that the nature of the eccentric structure is that two elements with different aspect ratios are being combined at θ=90°, and this articulation leads to non-standard Kenics static mixers with different underlying logic, which finally result in the differences between the PLS model and the univariate analysis.