Association of OPRK1/OPRM1 methylation with MCI in Uygur and Han groups was focused. DNA methylation was measured using bisulphite pyrosequencing method. A female-specific hypermethylation of OPRK1 in Han MCI group was identified. OPRM1 methylation was differently associated with MCI in Xinjiang Uygur and Han. Promoter fragments of OPRK1 and OPRM1 were able to upregulate gene expression.