In a hypoxic environment, hypoxia inducible factor 1 (HIF-1) plays a major role as a transcription factor that regulates the expression of many related genes, including those involved in angiogenesis, cell proliferation, apoptosis, and energy metabolism, so that organisms can adapt to an anoxic environment. Two full-length HIF-1 cDNAs (SpHIF-1 alpha and SpHIF-1 beta) from Scylla paramamosain Estampador, 1950 are reported. The cDNA of SpHIF-1a is 4,059 bp, including a 5' untranslated region of 267 bp, an open reading frame (ORF) of 3,180 bp coding for a protein consisting of 1,059 amino acids, and a 3' untranslated region of 612 bp. SpHIF-1 beta is 2,244 bp in length encoding a protein of 656 amino acids, with a 5' untranslated region of 150 bp and a 3' untranslated region of 123 bp. SpHIF-1 alpha consists of a signal peptide with 16 amino acids. Both SpHIF-1 alpha and SpHIF-1 beta have two conservative structure domains, which are basic helix-loop-helix (bHLH) and Per-Arnt-Sim (PAS) domains, whereas HIF-1 alpha exclusively has an oxygen-dependent degradation (ODDD) domain and a C-terminal transactivation domain (C-TAD), both playing crucial roles in hypoxia. SpHIF-1 alpha and SpHIF-1 beta were constitutively expressed in all of the experimental tissues in a normoxic environment, as detected by using qRT-PCR. The results indicated that 1) there was a synergistic effect between various tissues in the oxygen balance mechanism, such as the gills, the hepatopancreas and the hemocytes; 2) S. paramamosain could only tolerate 2 mg/l hypoxia; 3) hemocytes could be the last line of defense to maintain the oxygen balance and determine the minimum concentration of dissolved oxygen that an individual can bear; and 4) within nine hours in hypoxic conditions, individuals were not in a life-threatening situation. In summary, the HIF-1 gene plays an essential role in regulating the hypoxic response.