The hypoxia-inducible gene 1, YGHL1 from olive flounder (Paralichthys olivaceus) (fYGHL1) was cloned, and its structural organization and expression profiles were determined. A 1,400 kb full-length cDNA encoding a predicted polypeptide of 91 amino acids was sequenced. The fYGHL1 gene comprises three introns, four exons, and several transcriptional elements upstream of the transcriptional start site. The mRNA transcript is expressed in almost all tissues, with high expression in the intestine and brain of normal-conditioned fish, and is expressed constitutively in early developmental stages after hatching. The mRNA expression of fYGHL1 is highly regulated by hypoxia and E. tarda infection. The expression of fYGHL1 mRNA was down regulated in the gill, spleen, intestine, and stomach of flounder under hypoxic conditions, whereas the expression level was increased in flounder embryonic cells treated with the hypoxia-mimic CoCl(2) (a HIF-1 inducer). Pathogen challenge induced fYGHL1 expression in the spleen of juvenile fish. Taken together, these results suggest that fYGHL1 is a hypoxia-related gene with potential roles in the hypoxia response mechanism as well as in defense, immune responses, growth, and regulation of reproduction.