Single nucleotide polymorphism (SNP) rs11671784 is in the loop of pre-miR-27a and the G/A variation can significantly decrease mature miR-27a expression. This study explored the role of miR-27a in chemosensitivity of bladder cancer and how rs11671784 G/A variation affects the sensitivity. Blood and tumor samples from 89 bladder cancer cases were analyzed. In-vitro study was performed to explore the mechanism of chemo-sensitivity and the downstream target of miR-27a by using bladder cancer cell lines. This study identified a causative relationship between rs11671784 G/A variation, lowered miR-27a expression, increased RUNX-1 expression and following weakened chemo-sensitivity. rs11671784 G allele has significantly stronger effect over A allele in promoting chemo-sensitivity in bladder cancer. miR-27a mediates chemotherapy at least partially through reducing P-gp expression and increasing apoptosis. In addition, RUNX-1 is a novel direct target of miR-27a, which is involved in its regulation of chemo-sensitivity in bladder cancer. (C) 2015 Elsevier Inc. All rights reserved.