Stroke onset causes the majority of deaths and disabilities worldwide. There are two well-known forms of stroke. The first is hemorrhagic stroke, which is classified into two categories: Intracerebral and subarachnoid haemorrhage (Brønnum-Hansen et al., 2001; Zhakhina et al., 2022). The second type is ischemic stroke which represents 71% of all strokes over the world and is known as infarction of the brain, spinal cord, or retina (Brønnum-Hansen et al., 2001; Zhakhina et al., 2022). As a result, several studies focused on the pathological characteristics of ischemic stroke and its treatment. Thromboembolism is the most prevalent cause of ischemic stroke, whether from atherosclerosis or heart illness (Rinde et al., 2016; Rothwell, 2007). Additionally, elevated blood pressure, diabetes mellitus, as well as small vessel disease, can cause an ischemic stroke (Y. Ma et al., 2020; Maida et al., 2022). Secondary causes of pathological occurrence include patent foramen ovale (PFO) with paradoxical embolism, arterial dissection, vasculitis, and haematological diseases (Lucà et al., 2023; Namazi et al., 2011). Also, oxygen level depletion (hypoxia) has been reported as one of the causes of stroke due to the sensitivity of the central nervous system (CNS) to hypoxia (Elena V. Mitroshina, Maria O. Savyuk, Evgeni Ponimaskin, & Maria V. Vedunova, 2021; Namazi et al., 2011). In this review, we deeply focused on the relation between HIF-1 and different molecular reactions including inflammation, oxidative stress and autophagy. Besides, the dual role of HIF-1α has been highlighted. Meanwhile, a details investigation of the interaction between the HIF-1 pathway and other pathways such as pVHL, Ca+, MAPK, CK2 and JAK/Stat. Additionally, the role of HIF-1 in different brain cells also has been discussed.