Background In acute myeloid leukemia (AML), many genes have been studied as prognostic markers. SALL4 is expressed constitutively in human leukemia cell lines and primary AML cells. BMI-1 is expressed highly in purified hematopoietic stem cells (HSCs), and its expression declines with differentiation. Objective To study the expression levels of SALL4 and BMI-1 and their clinical significance in patients with AML. Methods The study was performed with 60 patients newly diagnosed with AML and 50 control individuals. SALL4 and BMI-1 expression detection were performed using real-time polymerase chain reaction (PCR). Results The expression of SALL4 and BMI-1 was significantly higher in cases of AML and showed a strong association with failure to achieve complete remission (CR) or with relapse (P = .02, P = .03, respectively). In multivariate analysis, these genes were the most powerful independent predictors of poor prognosis (P = .01 for SALL4, P = .02 for BMI-1). Conclusion SALL4 and BMI-1 are significant prognostic factors in AML and could be strong targets for novel types of therapy.