As cancer is one of humanity’s biggest killers in the world, scientists have been looking for different drugs as agents to treat cancer. However, current chemotherapeutics is not sufficiently effective. Thiosemicarbazone complexes of transition metals have attracted wide attention due to a great effect of anticancer activity with different mechanisms including ribonucleotide reductase inhibition, metal dependent radical damage, DNA binding, and inhibition of protein synthesis, and so on. In this minireview, we summarize different metal chelators of thiosemicarbazones and their anticancer mechanisms, which are useful for the development of thiosemicarbazone as anticancer drugs.