Objective:To explore the prognostic significance of NPM1,CEBPA,FLT3-ITD and c-kit gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML). Methods:Bone marrow (BM) samples of 112 patients with CN-AML were collected. Mononuclear cells (MNCs) were extracted and genomic DNA was isolated from BM specimens. Chromosome specimens were prepared using the direct method and short-term culture without phytohemagglutinin and the metaphase chromosomes were banded via improved heat treatment Giemsa R-banding method. Incidence of NPM1,CEBPA,FLT3-ITD and c-kit gene mutations was analyzed using genomic PCR and sequencing. Clinical characteristic,overall survival (OS),disease-free survival (DFS) and cumulative incidence of relapse rate were compared between gene mutant and wild-type patients. Cox regression analysis was performed to estimate the significantly prognostic factors for OS. Results:Incidence of NPM1,CEBPA,FLT3-ITD and c-kit mutation was 21.4%,21.4%,13.4% and 5.4%,respectively. WBC count of the patients with mutational NPM1 was significantly higher than that with wild-type NPM1. Patients with mutant FLT3-ITD or c-kit had significantly lower PLT,higher PB and BM blast proportion than those with wild-type genes. After excluding the patients giving up treatment and undergoing allo-SCT,patients with isolated NPM1 mutations had significantly better OS compared to wild-type patients. Patients with isolated mutated CEBPA had significantly better OS and DFS compared with the wild-type patients. Patients with CEBPA mutation had a significantly lower cumulative relapse rate than the wild-type patients. Cox regression analysis showed that age and BM blast proportion were independent prognostic factors for OS,and CEBPA mutations were associated with OS. Conclusion:FLT3-ITD and c-kit mutations were associated with lower PLT count and higher blast proportion in PB and BM. Isolated NPM1 and CEBPA mutations were associated with better prognosis in CN-AML.