Deep-sea hydrothermal vents are very extreme environments. Bythograeidae crabs are considered the most common and abundant species and predators at the top of food chain in the hydrothermal vent ecosystem. However, the genetic basis for the adaptation of hydrothermal vents crabs to the harsh environment remains poorly explored.The objectives of this study were to increase our understanding of the mechanisms of hypoxia adaptability in vent crabs and to confirm if there is a correlation between mitochondrial protein coding genes (PCGs) and adaptation to the extreme hydrothermal vent environment.Thirteen PCGs from mitochondrial genomes of 48 Brachyura species and one Diogenidae species were examined. Each of the genes was investigated and compared to orthologous sequences using PAML, Datamonkey, and TreeSAAP. Nine mitochondrial PCGs (ATP6, ATP8, COX1, COX3, CYTB, ND1, ND2, ND4, and ND5) were validated to have undergone positive selection (i.e., directional selection) in vent crabs by at least two methods. A series of putatively selected codons was localized in or close to the important functional regions (protein binding region and helical transmembrane region) in the mitochondrial protein structure.These results help explain why Bythograeidae crabs are capable of living in the hydrothermal vents and suggest that these crabs might have acquired an enhanced capacity for energy metabolism in an extreme hypoxic environment. These findings highlight the critical role of PCGs in the evolution of extreme environmental tolerance by Bythograeidae crabs.