Our data show that HOXA11-AS upregulates NQO1 expression by sponging miR-494 and downregulates NQO2 expression by EHZ2-mediated H3K27 trimethylation; overexpression of NQO promotes malignant phenotypes by promoting glutaminolysis, and suppression of NQO2 expression enhanced cancer stemness by increasing intracellular NAD levels. Here, HOXA11 is linked to cancer.