Curcumin is a natural dietary polyphenol extracted from turmeric plants. It has various functions， including antioxidation， anti-inflammation and anti-cancer. However， its biological functions and the underlying mechanisms remain to be elucidated. This study aimed to address whether antioxidation of curcumin is mediated by epigenetic regulation （such as microRNA）. The results showed that curcumin increased the antioxidative activity of LO2 cells， including reducing the ROS levels， increasing the total cellular antioxidant capacity and the activities of antioxidant enzymes， such as SOD， CAT and GSH-Px. Interestingly， we found that curcumin regulated the expression of let-7d-5p， which affected cell antioxidant capacity. These data indicated that let-7d-5p mediated the antioxidation of curcumin， which provided evidence for epigenetic-regulations of functional food components.