In this study, the ELP sequence was fused to human interferon-γ (hIFN-γ) and hIFN-γ-ELP fusion protein accumulated with high levels of yield and purity, compared with the corresponding unfused hIFN-γ protein. The hIFN-γ was exclusively produced in the form of insoluble inclusion bodies while the hIFN-γ was relatively soluble when expressed as an ELP fusion protein. The insoluble inclusion bodies were then solubilized under denaturing conditions, refolded in the presence of arginine and purified by single-step ion-exchange chromatography. The fusion to ELP signidficantly increased the accumulation of hIFN-γ by 10-fold with a stable expression on average of 46.85% of total soluble protein (TSP). Furthermore, three rounds of Inverse Transition Cycling (ITC) purification increased overall purity of the hIFN-γ-ELP to 98 ± 5%. The recovery amount of the fusion protein found to be dependent on the NaCl concentration, with increase of NaCl concentration, a greater fraction of the hIFN-γ-ELP was aggregated. However, due to the presence of an aliphatic guest residue in ELP sequence, the high concentration of salt was necessary to trigger the inverse phase transition of hIFN-γ-ELP fusion protein. Moreover, recombinant hIFN-γ and hIFN-γ-ELP proteins purified from E. coli possessed a relatively similar bioactivity based on viral cytopathic assay. Copyright © 2019 Elsevier Inc. All rights reserved.