Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting the elderly people. AD is characterized by progressive and gradual decline in cognitive function and memory loss. While familial early-onset AD is usually associated with gene mutations, the etiology of sporadic late-onset form of AD is largely unknown. It has been reported that environmental factors and epigenetic alterations significantly contribute to the process of AD. Our previous studies have documented that chronic hypoxia is one of the environmental factors that may trigger the AD development and aggravate the disease progression. In the past few years, we have conducted a series of investigations to determine the pathological effects of chronic hypoxia on the onset and development of AD and identify the possible molecule mechanisms underlying the chronic hypoxia mediated AD pathogenesis. Based on our studies we propose that epigenetic regulation is the key player in the chronic hypoxia-mediated neurodegeneration in Alzheimer’s disease, which may represent new opportunity for the therapeutic intervention of this disease.