Mitochondrial respiratory chain disorders (MRCD) are a large group of disorde rs that can affect any organ besides muscles or the central nervous system. We r eport two children who presented with neonatal cholestasis and progressive cirrh osis, who subsequently developed hepatocellular carcinoma (HCC). This suggests a particular risk of degeneration in these patients and the importance of a regul ar screening for secondary liver cancer. Suggestion of HCC should lead to early liver transplantation, which was successful without tumor recurrence in the two patients. Mitochondrial respiratory chain disorders (MRCD) are a large group of disorde rs that can affect any organ besides muscles or the central nervous system. Were eport two children who presented with neonatal cholestasis and progressive cirrhosis, who who developed hepatocellular carcinoma (HCC) This suggests a particular risk of degeneration in these patients and the importance of a regul ar screening for secondary liver cancer. Suggestion of HCC should lead to early liver transplantation, which was successful without tumor recurrence in the two patients.