Ganoderic acid (GA) is a kind of important bioactive triterpenoid with anti-cancer effect. 7-O-Ethyl ganoderic acid O (7-O-ethyl GA-O) was recently found to be a promising target for mass production of bioactive individual GA due to its high content. However, its apparent degradation was observed during preparation procedures. In this research, to understand and control its degradation process during the preparative isolation, a systematic kinetic investigation on 7-O-ethyl GA-O stability was done not only under different conditions of pH and temperature, but in different solvents as well. 7-O-Ethyl GA-O was proved to possess an optimal stability in neutral and non-polar environment. Its degradation kinetics and thermodynamics could be effectively described by first-order reaction model and Arrhenius equation. The activation energy was estimated to be 38.2±3.6kJ/mol in acidic methanol (0.01mM HCl, pH=5.1), 103.2±2.4kJ/mol in aqueous methanol (20% water), and 105.8±3.3kJ/mol in methanol. Furthermore, the possible mechanism of acid-catalyzed 7-O-ethyl GA-O decomposition in methanol was proposed, consisting of a fast protonation, followed by a committed step of ethanol removal.