PBX1 was abnormally overexpressed and its intracellular localization was found to be frequently amplified in many types of cancer, including renal clear cell carcinoma. PBX1 displays oncogenic activity in several different types of cells, but little is known about how signaling pathways are altered, and the function of PBX1 in renal clear cell carcinoma has not been well investigated. In this study, we demonstrate that the expression of PBX1 was significantly upregulated in 30 pairs of human tissues compared to adjacent normal tissues and the overall survival rate of PBX1-high group was significantly worse than that of PBX1-low group. Furthermore, JAK2 expression is significantly correlated to PBX1 expression in human clinical specimen and PBX1 knockdown inhibits STAT3 phosphorylation and reduced transcription of STAT3 target genes Cyclin Dl. More interestingly, PBX1 knockdown inhibits ccRCC cell viability, proliferation and cell cycle progression in vivo and in vitro. Thus, our results demonstrate that PBX1 plays an oncogenic role in ccRCC via JAK2/STAT3 pathway and indicate its potential application for the treatment of human ccRCC in future. (C) 2018 Elsevier Inc. All rights reserved.