We report the structural and vibrational properties of anticancer drug cisplatin (cis-[Pt(NH3)2Cl(2)]) in gas phase, in solid phase, and in aqueous solution using density functional theory (DFT) calculations, quantum mechanical/molecular mechanical (QM/MM) molecular dynamics, and effective normal modes analysis. In contrast with the gas-phase case, asymmetric hydrogen bonding environments are found in both solid phase and aqueous solution. It is shown that the discrepancy of the molecular geometry between previous gas phase calculations and the X-ray crystal structure can be resolved by considering intermolecular hydrogen bonds in the calculations of solid phase. In addition, our simulations in solid phase and aqueous solution reveal that asymmetric environmental effects lead to several spectral features observed in experiments, such as the blue-shift in the N-H stretching region and the frequency splitting of NH3 symmetric deformation modes. Furthermore, a similar decoupling and localization of several vibrational modes of cisplatin is found in solid phase and aqueous solution, in comparison to those of O-H stretching modes of water molecules in liquid water [J. Phys. Chem. Lett. 2013 , 4 (19 ), 3245-3250].