Abstract: Objective To evaluate the prognostic factors in predicting relapse of childhood acute lymphoblastic leukemia (ALL) treated with CCLG-2008 protocol. Methods From December 1st 2008 and December 31st 2012, 358 patients diagnosed with ALL and treated with the CCLG- ALL 2008 protocol were enrolled in this study. All patients were followed up until September 1st, 2015. Prognostic impact of clinical features, response to treatment, biological features were analyzed and multivariate analysis of predicted value was performed by Cox- regression analysis. Results After treatment of CCLGALL 2008 protocol, 79 patients suffered from relapse. The relapse rate in the standard-risk, intermediate-risk and the high-risk groups were 13.3%, 17.6%, and 41.3% , respectively (P < 0.05). The number of very early relapse, early relapse and late relapse were 25, 29, 25, respectively, accounting for 31.6 %, 36.7 %, and 31.6 %. The relapse rates in patients in B-ALL with initial leukocyte counts >100×10⁹/L, non-remission in 15th day of induction (M3), the level of minimal residual disease (MRD) on 12w (12w-MRD) >10^-4 were significantly higher, their corresponding hazard ratio were 3.17 (1.58 ~ 6.36), 1.87 (1.07 ~ 3.30), and 1.90 (1.12 ~ 3.20), respectively (P < 0.05). Conclusions After treatment with the CCLG-ALL 2008 protocol, a relatively high relapse rate is observed in children with high-risk ALL. High initial leukocyte counts, non-remission in D15-BM and 12w-MRD >10^-4 were the independent prognostic factors for childhood B-ALL.