It is widely accepted that aluminium is neurotoxic; it primarily causes cognitive dysfunction, which has been confirmed in human and animal tissue and cell experiments (Bondy, 2010), but its toxic mechanism has yet to be fully elucidated. Epigenetics is the study of changes in gene expression that may be triggered by both genetic and environmental factors and is independent from changes in the underlying DNA sequence, resulting in a change in phenotype without a change in genotype, which in turn affects how cells read genes. Some findings emphasize the potential significance of histone lysine methylation for orderly brain development and as a molecular toolbox to study chromatin function in vivo and in vitro. The H3K4-specific methyltransferase MLL is essential for hippocampal synaptic plasticity and might be involved in cognitive dysfunction. In the present study, we established that chronic aluminium exposure results in cognitive dysfunction, causing deficits in exploratory behaviour and learning and memory, in a dose- and time-dependent manner. Furthermore, we demonstrated in vivo and in vitro that chronic aluminium exposure reduces expression of histone H3K4 tri-methylation (H3K4me3) and the activity and expression of MLL. Taken together, these results indicate that chronic aluminium exposure may reduce H3K4me3 levels through suppressing activation of MLL, which in turn affects cognitive ability.