Abstract: Novel therapeutic approaches targeting key genes and regulatory molecules of hepatocellular carcinoma (HCC) have gradually been carried out in clinical practice. Hypoxia-inducible factor (HIF), as a critical factor for hepatocellular carcinoma cells to adapt to the hypoxic microenvironment, mediates changes in the transcription of many genes. HIF has a wide range of target genes and can promote metabolic reprogramming, angiogenesis, invasion and metastasis, and immune escape of cancer cells by regulating various signaling pathways. Hypoxia-inducible factor 1α (HIF-1α), as the main member of the HIF family, can provide new ideas and insights for exploring potential targets for HCC treatment.