Whether long non-coding RNA (lncRNA) single-nucleotide polymorphisms (SNPs) affect prognosis of acute myeloid leukemia (AML) remains unknown. To search the association between lncRNA SNPs and AML outcomes, thirty tagSNPs in five lncRNAs were genotyped in 313 AML patients. Survival analysis indicated that GAS5 rs55829688 (T>C) was significantly associated with prognosis of AML (p=0.018). Patients with rs55829688CC genotype showed higher GAS5 expression in peripheral blood mononuclear cells (PBMCs) (p=0.025) and harbored a longer platelets recovery (p=0.040) than carriers of rs55829688T allele. In vitro study indicated that GAS5 promoter harboring the rs55829688C allele showed marginally increased reporter gene activity (p=0.019), and the promoter activity was increased by TP63 in a dose-dependent manner (P=0.001). Moreover, GAS5 higher expression predict shorter AML overall survival (OS), which validated in GEO GSE12417 dataset (p=0.011). In conclusion, rs55829688 polymorphism could increase GAS5 expression by interacting with TP63, which might aggravate the myelosuppression and in turn lead to poor prognosis in AML. Trail registration number: ChiCTR-PPC-14005297.