Adaptive evolution of 12 protein-coding mitochondrial genes in members of genus Homo (Denisova hominin (H. sp. Altai), Neanderthals (H. neanderthalensis) and modern humans (H. sapiens)) has been evaluated by assessing the pattern of changes in the physicochemical properties of amino acid replacements during primate evolution. It has been found that molecular adaptation (positive destabilizing selection) in Homo becomes apparent in the form of 12 radical amino acid replacements accompanied with statistically significant (P < 0.001) changes of physicochemical properties that probably had functional consequences. These replacements occurred at the stage of a common ancestor of Homo (in CO2 and CytB genes) as well as with the appearance of the common ancestor of Neanderthals and modern humans (in CO1 and ND5 genes). Radical amino acid replacements were mainly revealed in the cytochrome c oxidase complex IV and cytochrome bc1 complex III, thus coinciding with the general trend of increasing nonsynonymous changes in mtDNA genes coding subunits of complexes' III and IV proteins in anthropoid primates.