A complete solid-state study of the drug quinacrine dihydrochloride has highlighted the existence of two anhydrous phases and a tetrahydrate form, using water sorption experiments, thermal analysis techniques, and crystallographic studies. The tetrahydrate crystal obtained by crystal growth from a water/dioxane (80:20, v/v) solution has been characterized by single-crystal X-ray diffraction at 123 K. This phase is a complex three-dimensional hydrogen bonding network, including four water molecules and two free chloride ions, and crystallizes in the P1 space group. Because no filiation between the two hydrates has been evidenced yet, the dehydration–rehydration mechanism has been evaluated for the present study as a destructive–reconstructive process. Two related anhydrous phases were also characterized by X-ray powder diffraction and thermal analysis.