Oligonucleotides directed against the hypoxia-inducible factor-1.alpha. (HIF-1.alpha.) gene are provided for modulating the expression of HIF-1.alpha.. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the HIF-1.alpha.. Methods of using these compounds for modulation of HIF-1.alpha. expression and for the treatment of diseases associated with the hypoxia-inducible factor-1.alpha. are provided. Examples of diseases are cancer and pre-eclampsia. The oligonucleotides may be composed of deoxyribonucleosides, a nucleic acid analogue, or Locked Nucleic Acid (LNA) or a combination thereof.