The possibilities of hydrolysis of low-boiling organic chlorides in crude oil to generate a corrosive component, namely, hydrogen chloride was evaluated by using thermodynamic analysis under the operating conditions of crude oil distillation in refinery. Thermodynamic analysis was performed based on a previous work about the identity of chlorides and their distribution in YS crude oil of China. The Gibbs free energy change of the hydrolysis was estimated using the specified concentrations of steam and chloride hydrolysis products, and the results indicated that the low-boiling organic chlorides could hydrolyze to corrosive hydrogen chloride during atmospheric and vacuum distillation of crude oil from a thermodynamic point of view. Thermodynamic analysis results also showed that a high temperature and a low pressure are advantageous to the hydrolysis reaction of low-boiling organic chlorides. This thermodynamic analysis is helpful to understand the mechanism for the generation of hydrogen chloride during crude oil distillation as hydrogen chloride can cause serious corrosion.