With the prevalence of obesity and metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the largest chronic liver disease in China. However, the pathogenesis of NAFLD remains unclear, and recent studies have found that interleukin-10 (IL-10) not only plays an important role in the pathogenesis of autoimmune diseases, inflammatory diseases, and malignant tumors, but also plays a key regulatory role in the pathogenesis of NAFLD. This article reviews the protective mechanism of IL-10 against NAFLD and its prospect in treatment, so as to further explore the clinical value of IL-10 in the diagnosis and treatment of NAFLD.