Thiosemicarbozone complexes that have a broad spectrum of biological activity are formed as a result of condensation reaction between thiosemicarbazide [H2N(C=S)-NH-NH2] and carbonyl-containing compounds. A new nickel(II) complex with N1-acetylacetone-N4-4-methoxy-salicylidene-S-allyl-thiosemicarbazone ligand was synthesized and characterized. We studied the antileukemic activity of the Ni(II) thiosemicarbazone compound and assessed their potential for drug development. Specifically, the effects of this Ni(II) thiosemicarbazone compound on intracellular signal nodes and apoptotic pathways were investigated. According to our results, the Ni(II) thiosemicarbazone compound has apoptotic activity against HL60 cells. Moreover, while Ni(II) thiosemicarbazone compound significantly increased levels of p53 and cleaved caspase-3 proteins, it decreased level of Phospho-Akt1 protein in HL60 cells. The Ni(II) thiosemicarbazone compound could induce HL60 cell apoptosis through inhibiting of PI3K/Akt pathway. These results showed that Ni(II) thiosemicarbozone compound might be an antileukemic agent.