The thermodynamic and kinetic properties for the nonenzymatic N-glycosidic bond cleavage in cis-(5R,6S)5,6-dihydroxy-5,6-dihydrodeoxythymidine (deoxythymidine glycol, dTg) were studied by computational techniques. Optimized structures for all of the stationary points in the gas phase were investigated using the BHandHLYP/6-311++G(d,p) and B3LYP/6-311++G(d,p) methods. Single-point energies were determined employing the ab initio MP2 method in conjunction with the 6-311++G(d,p) basis set, For the unimolecular decomposition of dTg in the gas phase, two pathways were characterized. Subsequently, the hydrolysis of dTg by a single water molecule was investigated. Two possible pathways were considered, involving the abstraction of the C2' hydrogen followed by the attack of water on the C1'=C2' bond (S(N)1 pathway) and the attack of a water molecule on the C1' atom with the simultaneous cleavage of the glycosidic bond (S(N)2 pathway). However, both the unimolecular decomposition reaction and the hydrolysis reaction involve large energy barriers, suggesting that the role of water is not beneficial to the overall reaction and the direct involvement of a sole water molecule as a nucleophile is unlikely. This result emphasizes the important catalytic role of enzymes. In addition, the solvent effect of water on the four processes was assessed at the geometry optimization level by means of the conductor-like polarized continuum model. Single-point computation was done at the MP2/6-311++G(d,p)//BHandHLYP/6-311++G(d,p) level. The calculated results show that the presence of the solvent water substantially lowers all energy barriers. Our results give out a greater fundamental understanding of the effects of the nucleophile water and solvent water for this important biological reaction.