Special AT-rich sequence-binding protein-1 (SATB1) has been recently reported to be overexpressed in various cancers and associate with the malignant behavior of cancer cells. However, the expression and potential roles of SATB1 in bladder cancer remains unclear. In the present study, SATB1 expression was analyzed in 85 archived bladder cancer specimens using immunohistochemistry and the correlations between SATB1 expression and clinicopathological parameters were evaluated. To further explore the biological functions of SATB1 in bladder cancer, siRNA knockdown was performed in 5637 and T24 bladder cancer cell lines. We then carried out CCK8 assay and examined cisplatin-induced apoptosis to address the roles of SATB1 in proliferation and apoptosis. We found that SATB1 was overexpressed in 33 of 85 (38.8 %) bladder cancer specimens. SATB1 overexpression associated with tumor grade (p = 0.002) and tumor stage (p = 0.027). SATB1 depletion in 5637 and T24 cells decreased cell proliferation while upregulating cisplatin-induced apoptosis. Further study demonstrated that SATB1 knockdown decreased cyclin D1 and cyclin E expression and upregulated caspase3 cleavage. In conclusion, SATB1 is overexpressed in bladder cancer and regulates malignant cell growth and apoptosis, which makes SATB1 a therapeutic target candidate for bladder cancer.