Acute liver failure (ALF) in children is a severe disease with a high mortality rate. The current treatment strategies are still defective, with many cases die when liver transplantation is unavailable. The current protocol of steroids therapy improved the survival rate of hepatitis A virus (HAV)-related ALF. However, there is still a high mortality for non-HAV cases. Stem cell therapy (SCT) has been tried in experimental animals with ALF and in few adult studies with acute-on-chronic liver failure. No previous trials of SCT have been tested in children with ALF. The absence of SCT application in ALF in children could be due to some issues. These could be related to safety, sources, administration route, optimum dosage, efficacy, and survival. It is proposed that could be the future therapy if these obstacles have been well studied and solved.