We made a diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency with a new mutation of 848A→G (exon 8) in a 16-year-old male patient presenting with severe hemolysis. He was administered a diclofenac sodium suppository (50 mg) at the time of first visit to our hospital because of pyrexia. In the acute phase, pyrexia, severe general fatigue, lumbar back pain, hemoglobinuria, and jaundice developed. Laboratory blood examinations showed hemolysis, and remarkable increases in serum ferritin and cytosol leucine aminopeptidase levels. Serum interleukin-6 and interferon-γ levels were also increased. No liver injury was found. He had neonatal jaundice persisting over 3 weeks. He did not have a history of chronic hemolysis or hyperbilirubinemia. Increases in serum ferritin or cytosol leucine aminopeptidase levels in G6PD-deficient patients were not reported earlier. In this case, it is presumed that infection and administration of anti-inflammatory agents induce the hemolytic episode and that hypercytokinemia deteriorates the disease condition.