It is difficult to predict the prognosis or clinical course of secondary hemophagocytic lymphohistiocytosis (HLH) due to the various underlying causes. The authors analyzed the clinical and laboratory findings and outcomes in patients with HLH who had initially been diagnosed with Kawasaki disease (KD), and evaluated the clinical significance of each factor. Among the 21 patients with HLH, 5 had initially been diagnosed with KD and 16 had other etiologies. A comparative analysis was performed for fever duration, presence of cytopenia, serum ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride, fibrinogen, hyponatremia, reactivation, and survival rate in those HLH patients associated with KD (group I) and other causes (group II). In patients in group I, a higher level of reactivation (20%), a lower survival rate (P = .001), higher AST (P = .031) and ferritin (P = .005), and frequent hyponatremia (P = .000) were found compared to patients in group II. Interestingly, patients in group I was older than the average of age of most KD patients. A high index of suspicion on the progression from KD to HLH would be mandatory when the KD patients show elevated AST and ferritin and the presence of hyponatremia, and especially so if the patient is of older age.