Background:Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. BAFF is member of TNFSF13B whose level is elevated in cases of ALL. Aim: To assess serum BAFF level in children with ALL and correlate its level with the clinical, laboratory findings and known prognostic factors as well as its relation to response to treatment.Subjects and Methods: This study was conducted at Zagazig University Hospitals in the period from April 2018 to June 2019 on 24 Egyptian children with newly diagnosed ALL and 24 apparently healthy children of matched age and sex as a control group. Patient history, clinical and laboratory examination results were taken, including complete blood count, bone marrow aspiration with cytochemistry, immunophenotyping, and estimation of serum BAFF level using ELISA kits.Results: We found statistically significant higher BAFF levels among de novo childhood acute lymphoblastic leukemia patients compared with the apparently healthy control group (P value < 0.0001).High serum BAFF was significantly correlated to patients' poor treatment response(P value < 0.05) but not patients' outcome (P value > 0.05).Conclusion: We found a significant relation between serum BAFF level and response to treatment so assessment of serum BAFF level at the time of diagnosis may be a predictor for response to treatment. This finding recommends that patients with high BAFF level at the time of diagnosis be subjected to intensified course of therapy.