Background The micro RNA (miRNA)/histone deacetylase 9 (HDAC9) signaling axis has been reported to be involved in initiating and developing multiple malignant tumors. In the present study, we aimed to determine whether miR-211-5p serves as a post-transcriptional regulator in bladder cancer (BCa) cell proliferation and apoptosis by targeting HDAC9. Methods miRNA expression profiling of BCa tissues and para-carcinoma tissues was screened by miRNA microarray. After transfection with miR-211-5p mimics or short hairpin RNA of HDAC9 (sh-HDAC9), mRNA and protein expression was evaluated using a quantitative reverse transcription-polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm was used, and a dual-luciferase reporter assay was performed to validate HDAC9 as a direct target of miR-211-5p. Cell proliferation was analyzed by the 3-(4, 5-dimethylthiazl2-yl)-2,5-diphenyltetazolium bromide (MTT) assay. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) detection was used to evaluate apoptosis in 5637 and T24 cells. A transwell assay was used to assess migration and invasion. Results miR-211-5p is down-regulated in BCa tumor tissues and cell lines. miR-211-5p is identified as an independent biomarker for predicting overall survival. HDAC9 is a direct target of miR-211-5p, and overexpression of miR-211-5p represses HDAC9 protein expressionin vitro. Overexpression of miR-211-5p or HDAC9 knockdown significantly inhibits proliferation, migration and invasion of 5637 and T24 cells, and also induces cell apoptosis. Conclusions miR-211-5p may play a role as a tumor suppressor and as a favourable prognostic marker in BCa.