Abstract: The hydrolytic deamination reaction mechanism of guanine (G) and nH2O (n=1、2) have been theoretically investigated including solvent effects at the B3LYP/6-31G** levels. The results showed that the hydrolytic deamination reaction of G may proceed two steps. The first step was rate-controlling, and the second step belonged to an internal hydrogen transfer reaction. The study of the potential energy surface showed that the deamination reaction of G-nH2O did not took place because of a higher barrier for the rate-controlling, which was agreement with the experimental result. In addition, one water molecule acted as catalyst for the deaminaiton reaction of G and 2H2O.