Nonalcoholic fatty liver disease (NAFLD) is associated with lipid accumulation in hepatocytes and advances into NASH. A recent study implicated that STARD10 gene expression is epigenetically regulated by methylation in the liver of NAFLD patients. We found that STARD10 is highly expressed in the liver and STARD10 knockout mice (Stard10^-/-) are resistant to develop fatty liver when fed high fat diet. Therefore we hypothesized that Stard10^-/- is resistant to develop NASH. Aimig at elucidating the hypothesis, we induced NASH model by choline deficient diet and compared the lipid accumulation in the liver between wild type (WT) and Stard10^-/- mice. Total lipid droplet area of Stard10^-/- mice was significantly smaller than that of WT mice. Gene expression levels of proinflammatory cytokines and fibrosis marker genes were significantly lower in the liver of Stard10^-/- mice compared with WT mice. It is well known that cytokines released from Kupffer cells promote NASH. However, Stard10 was not expressed in Kupffer cells. We also confirmed that there was no difference in the lipopolysaccharide-induced gene expression of proinflammatory cytokines in the Kupffer cells or macrophages between WT and Stard10^-/- mice. In conclusion, the disruption of STARD10 prevented the liver from developing NASH through the reduced accumulation of lipids.