Abstract: Objective　To explore the diagnosis and treatment strategy of Noonan syndrome accompanied by hematological symptoms of juvenile myelomonocytic leukemia. Method　The clinical data of one male neonate suffering from leukocytosis, mononucleosis and hepatosplenomegaly were retrospectively analyzed and the related literatures were reviewed. Results　The boy was born with symptoms, and was diagnosed with Noonan syndrome with PTPN11 mutation at the age of 3 months through the verification of nail, hair follicle, oral exfoliated cells, peripheral blood and bone marrow gene loci combined with special facial features and multiple organ congenital defects. He received low-intensity maintenance therapy and close follow-up. During the follow-up period to 9 months of age, the patient showed a tendency of spontaneous remission of hematological symptoms such as liver and spleen retraction and leukocyte decrease, while the PTPN11 mutation persisted in the peripheral blood of the patient. It has been reported that the incidence of Noonan syndrome is low, rarely with complications of blood system. It is difficult to differentiate Noonan syndrome from juvenile myelomonocytic leukemia. The hematological symptoms associated with Noonan syndrome are mostly self-limited. If no progress can be observed in close follow-up, no special intervention is required. Conclusions　Noonan syndrome accompanied by hematological symptoms is easily confused with juvenile granulocytic leukemia with syngenetic mutation. Family histories, special appearance, congenital defects, combined with multi-tissue gene validation are helpful for diagnosis.