In this study we evaluated children with newly diagnosed advanced (stage III and stage IV) mature B-cell non-Hodgkin lymphoma (B-NHL) or mature B-cell acute leukemia (B-AL), who were treated with Berlin-Frankfurt-Münster (BFM)95-based protocol combined with rituximab (R+BFM95). Our study recruited 46 patients who were treated with BFM95 protocol combined with rituximab. There are 23 patients as the historical control treated with BFM90 protocol. Compared with patients treated with BFM90 protocol, the 5-year event-free survival (EFS) rate of patients under R+BFM95 was higher (83.7%±5.7% vs. 69.6%±9.6%; P=0.1062). Among subgroups of our patients, the 5-year EFS of patients with stage III was 87.3%±6.1% vs. 77.8%±9.8% (P=0.2998), stage IV/B-AL was 72.7%±13.4% versus 40.0%±21.9% (P=0.0878) between patients treated with R+BFM95 and BFM90, respectively. Among patients whose lactate dehydrogenase (LDH) level were <500 U/L at diagnosis, R+BFM95 protocol reached 100% survival, nevertheless the 5-year EFS of patients in this group was not statistically different from that of patients treated with BFM90 (92.3%±7.4%; P=0.2994). Among patients had LDH≥500 U/L at diagnosis, the 5-year EFS in R+BFM95 group was 77.2%±7.7% (32 patients) and significantly higher than that of BFM90 group (40.0%±15.5%, 10 patients; P=0.0048). We found that rituximab has improved the EFS of childhood B-NHL/B-AL with LDH≥500U/L. Our results require validation from future studies with large cohort.