This study evaluated the efficacy and safety of a new regimen consisting of Topotecan, Ifosfamide, Etoposide, and L-asparaginase (TIEL) in treating aggressive T-cell lymphoma. Twenty-four patients were included in the research, eighteen males and six females. Half of the patients were in stages III and IV, and nearly half of them experienced failure of at least one regimen. Eleven were diagnosed as peripheral T-cell lymphoma (PTCL), five extranodal NK/T-cell lymphoma, non-specific, four angioimmunoblastic, and four anaplastic large-cell lymphoma (2 ALK positive). Patients were given 98 cycles of TIEL altogether. The responsive rate to TIEL was 76.9 % among 13 cases who received the regimen as the first-line treatment. Among 11 cases, TIEL was the second- or more-line treatment, the responsive rate was 63.6 %. The median PFS was 32.0 ± 21.0 (95 % CI 0-73.29) months. Median overall survival (OS) was not reached yet. Approximately 41.3 % of patients showed the third- to fourth-degree hematological side effects. Non-hematological toxicity included nausea, vomiting, diarrhea, and abnormal liver function. Among those patients received L-asparaginase, nine experienced mild abnormal coagulation function after 7 days of initiating chemotherapy, and no pancreatic injury was found. TIEL regimen is effective for aggressive T-cell lymphoma with controllable side effect and can be used for more patients.