Background: Pyroptosis, a programmed cell death (PCD) with highly inflammatory form, has been recently found to be associated with the origin of hematopoietic malignancies. Long noncoding RNA (lncRNA) had emerged as an essential mediator to regulate gene expression and been involved in oncogenesis. However, the roles of pyroptosis-related lncRNA (PRlncRNA) in acute myeloid leukemia (AML) have not yet been completely clarified.Methods: We collected AML datasets from public databases to obtain PRlncRNA associated with survival and constructed a PRlncRNA signature using Lasso-Cox regression analysis. Subsequently, we employed RT-PCR to confirm its expression difference and internal training to further verify its reliability. Next, AML patients were classified into two subgroups by the median risk score. Finally, the differences between two groups in immune infiltration, enrichment analysis and drug sensitivity were further explored.Results: A PRlncRNA signature and an effective nomogram combined with clinicopathological variables to predict the prognosis of AML were constructed. The internal validations showed that the PRlncRNA risk score model was an accurate and productive indicator to predict the outcome of AML. Furthermore, this study indicated that higher inflammatory cell and immunosuppressive cells, and less sensitive to conventional chemotherapy drugs were highlighted in the high-risk group.Conclusion: Through comprehensive analysis of PRlncRNA model, our study may offer a valuable basis for future researches in targeting pyroptosis and tumor microenvironment (TME) and provide new measures for prevention and treatment in AML.