The spectral tuning of halorhodopsin from Halobacterium salinarum (shR) during anion transport was analyzed at the molecular level using DFT-QM/MM [SORCI+Q//B3LYP/6-31G(d):Amber96] hybrid methods. Insights into the influence of Cl(-) depletion, Cl(-) substitution by N3(-) or NO3(-), and mutation of key amino acid residues along the ion translocation pathway (H95A, H95R, Q105E, R108H, R108I, R108K, R108Q, T111V, R200A, R200H, R200K, R200Q, and T203V) were analyzed for the first time in a fully atomistic model of the shR photoreceptor. We found evidence that structural rearrangements mediated by specific hydrogen bonds of internal water molecules and counterions (D238 and Cl(-)) in the active site induce changes in the bond-length alternation of the all-trans retinyl chromophore and affect the wavelength of maximal absorption in shR.