A hydrolysis process of the anticancer drug ImH[trans-Ru(III)Cl-4(DMSO)(Im)] (nicknamed NAMI-A; Im = imidazole, DMSO = dimethyl sulfoxide) has been studied by using density functional theory (DFT) method, and the aqueous solution effect has been considered and calculated by conductor-like polarizable calculation model (CPCM). The stationary points on the potential energy surfaces for the first and second hydrolysis steps (including two different paths) were fully optimized and characterized. The following was found: for the first hydrolysis process, the computed relative free energies Delta G degrees (aq) and rate constant (k) in aqueous solution are 23.2 kcal/mol and 6.11 x 10(-5) s(-1), respectively, in satisfactory agreement with the experimental values; for the second hydrolysis step, some disagreement still exists, and thus more accurate solvent model needs to be designed and improved. On the basis of our present limited work, it can reasonably suggest that the hydrolysis process of NAMI-A perform mainly via the first hydrolysis step and then the path 1 of the second hydrolysis step. The theoretical results provide the structural properties as well as the detailed energy profiles for the mechanism of hydrolysis of NAMI-A, such results may assist in understanding the reaction mechanism of the anticancer drug with the biomolecular target.