Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases of adults and its prevalence is increasing in children and adolescents. It is the most predisposing factor for liver cirrhosis. Due to complications of NAFLD, the treatment of this disease is essential. Since silymarin is recommended for adults recently, the effect of this herbal drug on children and adolescents was evaluated for treatment of NAFLD in children.Methods: This is a clinical trial study, which was done in Shahrekord University of Medical Science in 2012-2013 on 5-16 years old children with NAFLD. The patients were randomly divided into two groups containing 20 patients in each group. Silymarin tablets were administered for 12 weeks in case group and changing life style including exercise was advised in both groups. Liver sonographay and liver function tests (LFTs) were done after 12 weeks.Results: Patients with higher grade of fatty liver were developed lower grade of fatty liver during intervention in case group based on sonography after 12 weeks (P = 0.001). Meanwhile, no significant changes were observed in control group (P = 0.35). Liver enzymes (alanine aminotransferase ALT and aspartate transaminase AST) (P = 0.001, P = 0.025, respectively) and triglyceride (TG) levels (P = 0.043) were improved significantly but low-density lipoprotein (LDL) and high-density lipoprotein (HDL) did not change during intervention in case group.Conclusion: Silymarin can improve fatty infiltration of liver and liver function in children and adolescents