Objective To investigate treatment strategies and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL). Methods A retrospective cohort study enrolled 86 children diagnosed with and relapsed from ALL between 2015 and 2019. Kaplan-Meier method and Cox regression model were applied for analysis. Results The median follow-up after relapse was 36 months. The 4-year overall survival (OS) rate was 59%. Multivariate analysis (based on the subgroup receiving induction chemotherapy) identified high-risk relapse and minimal residual disease (MRD) ≥0.01% after induction therapy as independent risk factors for 4-year OS (P0.05). The introduction of chimeric antigen receptor T-cell (CAR-T) therapy in 2017 significantly improved the 4-year OS rate in children with relapsed ALL (61% vs 26%, P=0.030). According to relapse risk stratification, all low-risk patients survived whether receiving chemotherapy alone or CAR-T therapy. Among intermediate-risk patients, those achieving MRD negativity after re-induction had a high survival rate with chemotherapy (12/13), whereas MRD-positive patients had a high survival rate with CAR-T combined with transplantation (7/8). In high-risk patients, the survival rate for those receiving transplantation (after chemotherapy or CAR-T) was 60% to 62.5%, significantly higher than that of the chemotherapy-alone group (0% survival). The 4-year OS rate for the CAR-T followed by hematopoietic stem cell transplantation group was higher than that of the CAR-T alone group (75% vs 24%, P=0.067). Conclusions An individualized treatment strategy based on risk stratification combined with MRD status is recommended for children with relapsed ALL.