Background: Acute lymphoblastic leukemia (ALL) is the most common type of pediatric hematopoietic leukemia in children, accounting for 30-35% of all pediatric cancers. Abnormal miRNA expression has been reported to be related to cancers and other diseases , miRNA 146a rs2910164 polymorphism has been widely examined in various types of cancers including hematological cancers . Methods: This case control study was conducted on 80 children with ALL (group I) who are admitted at Benha University Hospital and Benha Specialist Hospital for Children and 40 healthy children with matched age and sex as controls (group II), we studied the miRNA-146a (rs2910164) polymorphism using Polymerase Chain Reaction-Restriction Fragment-Length Polymorphism (PCR-RFLP) approach. Results: Acute lymphoblastic leukemia (ALL) cases showed significantly higher proportions in GC, CC genotypes and C allele (40% for GG, 38.8% for GC, 21.2% for CC and 59.4% for G and 60.4% for C) (P= 0.023, 0.005,