Background: Tumor necrosis factor receptor type 1-associated death domain protein (TRADD) mediates programmed cell death signaling as well as the Fas-induced cell death pathway. The downregulation of TRADD is found to be associated with the occurrence of many cancers. The present study was designed to investigate the association between TRADD and clinico-pathologic features as well as its clinical significance in acute myeloid leukemia (AML). Methods: Real-time polymerase chain reaction was performed in 100 new AML, 23 AML complete remission patients, and 20 normal individuals. All statistical analysis was performed using SPSS software. Results: It was found that the expression of TRADD messenger RNA was lower in new AML patients as compared to healthy individuals and complete remission patients (P = 0.00239). Moreover, TRADD messenger RNA levels were associated with clinical factors such as risk classification (P = 0.0023) and complete remission (P = 0.0147). Kaplan-Meier analysis revealed that the AML patients with high TRADD expression had significantly prolonged overall survival and higher complete remission compared with low TRADD expressing patients. Conclusions: It is concluded that downregulation of TRADD may be an independent potential prognostic biomarker in AML.