Abstract: The hydrogen transfer reaction mechanism and potential energy surface of hypoxanthine(Hx) have been theoretically investigated using density functional theory (DFT) at the B3LYP/6-31G^** level, which included water as catalyst. The results showed that the H transfer reaction between enol form and keto form of Hx may take place via a cyclic transition state. (1) Without water as catalyst, the inner H transfer reaction may occur via 4-membered cyclic transition state. (2) With one water molecule as catalyst, the H transfer reaction of Hx involved 6-membered cyclic transition state. (3) With two water molecules as catalysts, the H transfer reaction of Hx belonged to an intermolecular H transfer reaction and its transition state is 8-membered cyclic structure. The study of the potential energy surface showed that H shift reaction may proceed more easily with two water molecules as catalysts. In addition, the effect of hydrogen bonds played an important role in increasing the stabilities of complexes on Hx with H₂O and lowering the activation energies of H shift.