Purpose: NUDT15 genetic polymorphism is known to be associated with frequent hematopoietic toxicities during acute lymphoblastic leukemia (ALL) mercaptopurine therapy. The aim of this study is to test this association in a group of Syrian children with ALL, in addition to quantify the prevalence of the corresponding SNP in patient population. Patients and Methods: This is a retrospective study that included all children with acute lymphoblastic leukemia reaching at least 6 months of maintenance therapy between January 2018 and May 2020 at two recruitment sites in Damascus, Syria. The NUDT15 rs116855232 genetic polymorphism was performed and linked to four clinical factors: mercaptopurine dose intensity, early onset leukopenia, hepatotoxicity and therapy interruption. Results: A total of 92 patients were enrolled (63.04% low-risk, 25% intermediate-risk and 11.96% high-risk). The TC genotype was found in 5 patients (5.4%) and the TT genotype was found in 1 patient (1.08%), with the following allele frequency: C=0.961 and T=0.038. The mercaptopurine dose intensity was 81.98%, 65.85% and 4.99% for the genotypes CC, TC and TT respectively (P: 0.0174). A significant association was found between early onset neutropenia and NUDT15 polymorphism (TC or TT), OR: 6.82 (95% CI: 1.22-38.11, P: 0.043). No association was found between NUDT15 polymorphism and therapy interruption or hepatotoxicity. Conclusion: Our study confirms that NUDT15 rs116855232 polymorphism is associated with mercaptopurine hematopoietic toxicity but not with hepatotoxicity or therapy interruption in a population of Syrian children with ALL. The incidence seems to be higher than neighboring countries.