Objective：This study aims to investigate the endoplasmic reticulum correlative protein 1 （Derlin-1） expression in non-alcoholic fatty liver disease（NAFLD）and its effect on PERK（protein kinase R-like ER kinase）signal pathway to inhibit NAFLD. Methods：The expressin of Derlin-1 in liver tissues of NAFLD mice was detected by immuhistochemical staining and Western blotting. The over-expression of Derlin-1 in HepG2 cell was performed by plasmid vector transfection. Derlin-1 inhibits PERK pathway detected by Western blotting. Results：The expression of Derlin-1 in liver tissues of NAFLD mice was increased compared with that in nomal liver tissues. Overexression of Derlin-1 inhibited endoplasmic reticulum stress pathway activition. Conclusion：High expression of Derlin-1 in liver tissues of NAFLD pratients may play a critical role in decreasing endoplasmic reticulum stress and inhibiting liver cell pemelosis through inhibiting PERK expression.