Training at high altitude for prolonged periods can cause low oxygen tension which can developed complication of hypoxia. Hypoxia is a cascade activity from a level of down regulation and function of cell’s nucleus. Early detection of biomarker and physiological changes are important in prevent the hypoxia at high altitude. Hyperbaric medicine is a new treatment that were used an oxygen therapy to treat hypoxic and inflammatory driven conditions which patients are treated with 100% oxygen at pressure greater than atmospheric pressure. The review discusses physiological changes associated with hypoxia, the response of biomarker hypoxia changes in high altitude and the role of hyperbaric oxygen therapy can play as part of the treatment for pilots and athletes training at high altitudes that suffering from disease with underlying hypoxia.