Rare autosomal-recessive disorder Chediak-Higashi syndrome (CHS) is characterized by cutaneous hypopigmentation which also affects hair and iris, recurrent bacterial infections, deterioration of intellectual functions and an increased risk of developing hemophagocytic lympho histiocytosis (HLH), which is characterized by pancytopenia, fever, and infiltration of the liver, spleen, and lymph node by lymphocytes and histiocytes with a dismal prognosis, HLH is an accelerated phase of CHS which requires challenging treatment, our case 13 years old female patient was diagnosed with Chediak-Higashi Syndrome, who had advanced HLH aggravated by viral infection HAV(hepatitis A virus), cytomegalovirus (CMV) infection, and autoimmune disease (systemic lupus erythematosus) (SLE), she developed neurological manifestations in the form of peripheral neuropathy large azurophilic granules in granulocytes were identified by Giemsa staining and silvery hair, abnormal hypopigmented dots scattered on her body more in the upper and lower limbs which is very important for the diagnosis of this syndrome. CHS should be differentiated from other causes of partial albinism such as Griscelli syndrome.