Objective: To measure the expression level of caspase 8 associated protein 2 (CASP8AP2) in newly diagnosed bone marrow childhood acute lymphoblastic leukemia (ALL) samples and analyze its associations with bone marrow relapse, disease free survival (DFS) as well as overall survival (OS). Materials and Methods: Fifty newly diagnosed ALL cases were evaluated using clinical and laboratory measures. CASP8AP2 expression was measured in bone marrow samples using real-time quantitative PCR (qRT-PCR). Another 25 blood samples from healthy reference control subjects with matched age and sex were also measured for CASP8AP2 expression. Results: Patients with high CASP8AP2 expression have significantly better OS (p value = 0.017) and DFS (p value = 0.018) than those with low CASP8AP2 expression. There was a significantly high bone marrow relapse rate in CASP8AP2 low-expression group with (p value = 0.018). From receiver operating characteristic (ROC) curve, the best cut-off values were established for CASP8AP2 for the prediction of development of relapse in the present study group was 0.319, with a sensitivity of 100% and a specificity of 91.3%. The area under the curve was 0.916. Conclusion: Relapse showed statistically low CASP8AP2 expression versus those who continued complete remission (CCR). So, CASP8AP2 expression was reported as an independent prognostic factor in childhood ALL.