The conformations of N-benzylideneanilines X-PhPhCH=NPh-Y were studied by B3LYP (DFT) hybrid method in combination with the 6-31G* split valence basis set. It was observed that the twist angle of the benzylidene ring or aniline ring with respect to the rest of the molecule (τ1 or τ2) estimated by the DFT method are highly reliable, and τ2 can be systematically regulated through X and Y substitution. The substituent effects on τ2 obtained from DFT calculations were investigated. It is demonstrated that substituent cross-interaction has a certain influence on τ2, and a quantitative model was proposed to express such an effect. The findings of the present study illustrate a practical method for expressing the relationship between substituents and molecular conformation of the X-PhPhCH=NPh-Y compounds.