Hypoxia-inducible factor-1 (HIF-1) has emerged as a significant target for cancer therapy due to its strong correlation with tumor metastasis, angiogenesis, poor patient prognosis, and resistance to therapy. HIF-1α, a key component of the HIF-1 pathway, is activated under hypoxic conditions to regulate essential biological processes in tumor cells. The HIF-1α pathway is regulated at multiple levels, including oxygen-dependent and oxygen-independent mechanisms, and involves post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation. Targeting the HIF-1α pathway has been challenging but promising, with several small molecules identified as potential inhibitors. These inhibitors act at different stages of the HIF-1α pathway, including mRNA expression, translation, stabilization, dimerization, DNA binding, and transcriptional activity. Despite the complexity of the HIF-1α pathway, ongoing research aims to develop more specific and effective inhibitors for cancer treatment.Hypoxia-inducible factor-1 (HIF-1) has emerged as a significant target for cancer therapy due to its strong correlation with tumor metastasis, angiogenesis, poor patient prognosis, and resistance to therapy. HIF-1α, a key component of the HIF-1 pathway, is activated under hypoxic conditions to regulate essential biological processes in tumor cells. The HIF-1α pathway is regulated at multiple levels, including oxygen-dependent and oxygen-independent mechanisms, and involves post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation. Targeting the HIF-1α pathway has been challenging but promising, with several small molecules identified as potential inhibitors. These inhibitors act at different stages of the HIF-1α pathway, including mRNA expression, translation, stabilization, dimerization, DNA binding, and transcriptional activity. Despite the complexity of the HIF-1α pathway, ongoing research aims to develop more specific and effective inhibitors for cancer treatment.