Fms-like tyrosine kinase 3 (FLT3) and Nucleophosmin1 (NPM1) mutations are the most common molecular variations in acute myeloid leukemia (AML) and have been associated with prognosis. The frequencies of FLT3, NPM1 mutations in the Algeria population remains unknown due to the lack of data related to this subject. Herein, we aim to investigate the prevalence of these mutations in our population and assess their prognosis impact. Adult AML patients (n= 60) were analyzed for FLT3-internal tandem duplication (ITD), D835Y point mutation and NPM1 exon12 mutations. FLT3-ITD was detected using polymerase chain reaction (PCR), D835Y mutation was detected by restriction fragment length polymorphism (PCR-RFLP) and NPM1 exon12 was detected by Sanger sequencing. The relation between the mutations and the clinical features of the patients was evaluated. FLT3 mutations were present in 11.6% and NPM1 mutations were observed in 15.09% of AML patients. The most frequent NPM1 mutation type was the “type-A mutation” (87.5%). Furthermore, a novel “indel” mutation was also detected in one patient. According to the statistical analysis results, FLT3mut group showed shorter survival time and poor response to the induction therapy, while NPM1 was a predictor of better prognosis in the absence of FLT3 mutations. Our results reveal that FLT3 and NPM1 mutations are less frequent in our population than reported in literature. Patients with isolated NPM1 and FLT3 mutation have different clinical features than those with combined mutations. NPM1 and FLT3 mutations can be used as prognostic factors in AML risk classification.