Solvent extraction of Ni(II) with CYANEX 301 "bis "2,4,4- trimethylpentyl" dithiophosphinic acid" in iso-dodecane from sulfate medium has been systematically investigated. In addition, a systematic investigation was conducted on the synergistic extraction behaviors of the mixed solvents consisting of CYANEX 301 and a series of extractants such as LIX 984, LIX 84-I, KELEX 100, and D2EHPA. It was elucidated that all of these mixtures could exhibit a good synergistic effect for extraction of nickel. Different parameters affecting the extraction process such as hydrogen ion, extractant, metal ion concentrations, and temperature were carried out. Maximum Ni(II) extraction was achieved in the equilibrium pH of 1.3 for all synergistic mixtures. The thermodynamic parameters, free energy (ΔG), enthalpy (ΔH), and entropy (ΔS), have been calculated. In particular, all synergistic mixtures appeared to be the most feasible and economic from a practical point of view yielding acceptable extraction and stripping efficiency for nickel and a low acidity requirement for stripping of nickel.