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Myocardial ischemia‑reperfusion injury (MIRI) is a severe injury to the ischemic myocardium following the recovery of blood flow. Currently, there is no effective treatment for MIRI in clinical practice. Over the past two decades, biological studies of hypoxia and hypoxia‑inducible factor‑1α (HIF‑1α) have notably improved understanding of oxygen homeostasis. HIF‑1α is an oxygen‑sensitive transcription factor that mediates adaptive metabolic responses to hypoxia and serves a pivotal role in MIRI. In particular, previous studies have demonstrated that HIF‑1α improves mitochondrial function, decreases cellular oxidative stress, activates cardioprotective signaling pathways and downstream protective genes and interacts with non‑coding RNAs. The present review summarizes the roles and associated mechanisms of action of HIF‑1α in MIRI. In addition, HIF‑1α‑associated MIRI intervention, including natural compounds, exosomes, ischemic preconditioning and ischemic post‑processing are presented. The present review provides evidence for the roles of HIF‑1α activation in MIRI and supports its use as a therapeutic target.