The structural basis behind the pungency of sanshools remains largely unknown at present. Herein, the crucial geometrical, electronic and energetic properties of sanshools have been explored and correlated with the pungency computationally. Our results have revealed the preferred reactive sites or area in sanshools responsible for their degradation, as well as their probable electrostatic and hydrophobic interaction patterns with the pungent receptors. Increasing the solvent polarity in the calculations or the conjugated CC numbers increase their chemical instability. The correlation between the polar/nonpolar/negative/positive surface area and pungency indicates the necessity of the amide, CC bonds, HO groups and carbon chains. The autoxidation may occur more probably through the radical addition than hydrogen abstraction during their applications like the process of relevant foods, and increasing the conjugated CC numbers weakens the corresponding allylic CH bonds. This study would benefit the mature pungent mechanistic understanding and practical applications in the pungent foods.