Hypoxia-inducible factor is a key factor in HIF signaling pathway and plays an significant role in Hypoxia response in animals. To determine the response of hypoxia-inducible factor (HIF-1) gene of Scapharca broughtonii under hypoxia stress and to reveal the unique hypoxia-adapting mechanism of Scapharca broughtonii. The cDNA sequence of HIF-1α (named ) by EST and RACE methods were obtained. The mRNA expression in the gene under hypoxia stress was also studied.Sequence analysis revealed that the cDNA was 2741 bp in length, including an open reading frame (ORF) of 2136 bp encoding a polypeptide of 711 amino acid residues with conserved HLH, PAS-A, PAS-B and PAC motif. The predicted molecular weight is 80.8 kDa and isoelectric point (pI) is 5.57. The analysis of structure and putative functional sites showed Chlamys farreri HIF-1 and the corresponding homologous molecule in mollusks clustered into one branch. The mRNA expression analysis of in tested tissues by quantitative real-time PCR (qRT-PCR) revealed that the mRNA of the the gene could be all detected in foot, gill, mantle, adductor muscle, haemocytes and hepatopancreas. The expression level of in haemocytes were more than that in other tissues. Under the hypoxic stress of 0.5 mg/L, 2.5 mg/L and 4.5 mg/L dissolved oxygen (DO) in seawater, SbHIF-1 in each tissue responded positively, and hemolymph and gill were more responsive than the other four tissues. n haemolymph, the expression of SbHIF-1 was significantly different from that of control group after 4 hours of DO stress ( reached the highest level, which was 519.43 times of that of control group. The response of each tissue to at different DO concentrations showed that the activation of SbHIF-1 was relatively high in 0.5 mg/L of the three treatment concentrations. This study clarified the structural characteristics, temporal and spatial expression characteristics of SbHIF-1 gene and its response to hypoxia stress, which enriched the research data of marine shellfish HIF gene.