Hypoxia is a critical pathophysiological stimulus and plays a pivotal role in the pathogenesis and progression of vascular diseases, particularly in the dysfunction of autologous arteriovenous fistula (AVF). The hypoxia-induced phenotypic switch of vascular smooth muscle cells (VSMCs) is a key step leading to vascular remodeling and other pathological alterations. Hypoxia promotes the transition of VSMCs from a contractile phenotype to a synthetic phenotype, resulting in vascular wall reconstruction, neointimal hyperplasia and ultimately compromised AVF patency. Although considerable researches on hypoxia-induced VSMCs phenotypic switch have been conducted in recent years, its molecular regulatory network remains intricate with many unresolved problems. This article systematically reviews molecular mechanism of VSMCs phenotypic switch under hypoxia, encompassing key signaling pathways, transcription factors and epigenetic regulatory features, and emphasizes their specific roles in AVF dysfunction and potential therapeutic targets, in order to provide theoretical support and research directions for better comprehension  of AVF pathology and for design of effective intervention strategies to maintain long-term and stable function of AVFs.