To investigate the role of lncRNA ZEB1-AS1 in B-lineage acute lymphoblastic leukemia (B-ALL). ZEB1-AS1 levels were aberrantly up-regulated in B-ALL. All correlated with STAT3 activation and IL-11 production. Moreover, a high level of ZEB1-AS1 predicted poor prognosis of B-ALL patients. Mechanistically, ZEB1-AS1 could bind to IL-11 and promote IL-11 stability. Down-regulation of ZEB1-AS1 decreased IL-11 production of human bone marrow stromal cells (BMSCs), which led to suppressed proliferation and inhibited IL-11/STAT3 pathway in BALL-1 cells. ZEB1-AS1 promotes the activation of IL-11/STAT3 signaling pathway by associating with IL-11 in B-ALL.