Abstract: Objective To compare the efficacy and safety of HyperCVAD regimen and CHOP regimen in treating patients with lymphoblastic lymphoma (LBL). Methods Seventy-five LBL patients were enrolled from January 2002 to October 2013, with 44 being treated with HyperCVAD and 31 being treated with CHOP regimen. The patients were followed up until 31 December 2013. Factors associated with the prognosis of the patients were analyzed using Logistic and COX regression models. Results The complete remission rate (73% vs. 23%) and overall response rate (91% vs. 46%) were both significantly higher in the patients receiving HyperCVAD regimen compared with those receiving CHOP regimen (P<0.000 1). The follow-up lasted on average (median) 9.9 months (ranging from 1.3 to 41 months). The patients receiving HyperCVAD regimen had significantly longer overall survival (OS) (median 31.5 vs. 11 months, P=0.012 7) and progression-free survival (PFS) time (median 16 vs. 5 months, P=0.000 4) than those receiving CHOP regimen. Complete remission (CR) was negatively associated with increased lactate dehydrogenase 〔LDH, standard partial regression coefficent (β)=-0.479〕 and international prognostic index (IPI score≥3, β=-0.691) in the patients receiving HyperCVAD regimen. The only significant predictor for survival was CR 〔relative risk (RR)=0.146，95% confidence interval (CI): 0.044-0.488〕. Common adverse events of the two regimens were bone marrow suppression, pulmonary infection, liver dysfunction and hemorrhage. Patients receiving HyperCVAD regimen were more likely to suffer from bone marrow suppression (100% vs. 84%) and severe pulmonary infection (27% vs. 3%) than those receiving CHOP regimen (P<0.05). No patient died of those adverse events. Conclusion Compared with CHOP regimen, HyperCVAD regimen can improve response rates and survival of LBL patients. Its higher level of pulmonary infection can be managed.