Because the impact of the full-scale substitution of Ca²⁺ in brushite (CaHPO₄·2H₂O) with Ni²⁺ ions has never been systematically explored, it is the focus of this investigation, as it holds potential for use in Ca_xNi_1−xHPO₄·nH₂O production. These biomaterials have many beneficial characteristics that can be modified to suit diverse applications, including bone tissue regeneration and pharmaceutics. For the present study, NaH₂PO₄·2H₂O, Ca(NO₃)₂·4H₂O, and Ni(NO₃)₂·6H₂O were used in various molar concentrations to obtain the required starting solutions. Previous studies have shown that adding Ni ions in the initial solution below 20% results in the precipitation of monophasic brushite with slight changes in the crystal structure. However, this study confirms that when the Ni ions substitution increases to 20%, a mixture of phases from both brushite and hexaaquanickel(II) hydrogenphosphate monohydrate HNiP (Ni(H₂O)₆·HPO₄·H₂O) is formed. The results confirm that the full replacement (100%) of Ca ions by Ni ions results in a monophasic compound solely comprising orthorhombic HNiP nanocrystals. Therefore, a novel technique of HNiP synthesis using the precipitation method is introduced in this research work. These materials are subsequently analyzed utilizing powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The obtained results confirm that the material microstructure is controlled by the Ni/Ca ratio in the starting solution and can be modified to obtain the desired characteristics of phases and crystals.