Interferon gamma (IFN-γ) is an important N-glycosylated protein produced primarily by T-lymphocytes and natural killer cells.[1] As a cytokine that is crucial for innate and adaptive immunity against viral infection, IFN-γ also exhibits anti-proliferative, immunoregulatory and proinflammatory activities.[2] Herein, we described our studies toward the synthesis of IFN-γ via an α-selective lysine ligation. The synthetic protein exhibits comparable anti-cancer activity to recombinant IFN-γ in an anti-proliferation assay.[3]