In recent years, neuroscience research has confirmed that the human immunodeficiency virus (HIV) may have adverse effects on brain function, involving mainly structural changes and cognitive impairment. Combination antiretroviral therapy reduces the prevalence of HIV-associated neurocognitive disorder (HAND), but the lighter, disabling HAND remains an unsolved challenge. The apolipoprotein E (ApoE4) gene, which is a common genetic variation in humans, is known to increase cognitive damage from HIV by affecting fat oxidation and cholesterol metabolism, accelerating the progression of and death from acquired immunodefciency syndrome (AIDS), and increasing susceptibility to opportunistic infections. Magnetic resonance imaging (MRI) has been widely used in the study of brain damage in HIV because it can clearly show brain structure and function. Moreover, MRI-related techniques can be used to detect the effects of the interaction between HAND and ApoE4 on cognitive impairment, but this complex mechanism needs to be further studied. This article reviews the current status of MRI neuroimaging research into the interaction mechanism between HAND and ApoE4.