The present invention relates to a method for substituting for or acting with the hyperbaric oxygen therapy to improve hypoxia, comprising the step of: administrating a phthalide compound to a subject in need thereof, wherein the phthalide compound can increase the oxygen release efficiency of blood hemoglobin (Hb) in the subject and further increase the cellular oxygenation level, and when the phthalide compound substitutes for or act with the hyperbaric oxygen therapy, the common adverse side effects of the hyperbaric oxygen therapy, such as barotrauma, decompression sickness and oxygen poisoning, are prevented. The phthalide compound is used to substitute for or act with 2,3-BPG, to modulate and decrease the oxygen affinity of hemoglobin (Hb), to increase the oxygen release efficiency of hemoglobin (Hb) to tissue cells, thereby achieving a normal cellular oxygenation level and maintaining the cellular oxygenation level in a normal range.