Abstract: Chronic kidney disease has become a major global public health challenge, and cardiovascular disease is the leading cause of death. Vascular calcification is characterized by pathological deposition of calcium and phosphate minerals in the arterial wall, which can lead to vascular sclerosis and lumen narrowing. This not only affects the blood supply to the kidneys, but also increases the risk of cardiovascular disease. In the pathological setting of chronic kidney disease, the kidneys are in a constant state of hypoxia. Hypoxia inducible factors 1 alpha (HIF-1α), as a key transcription factor, is essential for cellular adaptation to the hypoxic environment. HIF-1α affects the progression of vascular calcification in chronic kidney disease through multiple pathways, notably by encouraging osteoblast-like differentiation in vascular smooth muscle cells. Hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) is a novel oral treatment for renal anemia that can inhibit the degradation of HIF to promote erythropoiesis and increase endogenous erythropoietin production by activating the body’s natural physiological response to hypoxia. Studies have shown that HIF-PHI has the potential to promote vascular calcification, and its pro-calcification effects are closely related to the stability of HIF-1α. Therefore, it is important to fully understand the potential harmful effects of HIF-PHI in vascular calcification and pay attention to it.