A quantitative structure-property relationship (QSPR) study of the gas-phase lithium cation basicity of a diverse set of 205 compounds provided a general six-parameter QSPR model (R-2 = 0.801; R-cv(2) = 0.785; F = 133.11; s(2) = 8.78) using the CODESSA PRO program. Theoretical molecular descriptors, such as the minimum net atomic charge, highest occupied molecular orbital energy, total point-charge component of the molecular dipole, etc., logically explain the reaction equilibrium and electrostatic interaction between a lithium cation and a base.