The three homologous members of the p160 SRC family (SRC-1, SRC-2 and SRC-3) mediate the transcriptionalfunctions of nuclear receptors and other transcription factors, and are the most studied of all the transcriptionalco-activators. Recent work has indicated that the SRC-3 gene is subject to amplification and overexpression invarious human cancers. Some of the molecular mechanisms responsible for SRC overexpression, along with themechanisms by which SRC-3 promotes breast and prostate cancer cell proliferation and survival, have beenidentified. However, the function of SRC-3 in bladder cancer remains poorly understood. In the present study,our results indicate that overexpression of SRC-3 promotes bladder cancer cell proliferation whereas knockdownof SRC-3 results in inhibition. At the molecular level, we further established that CXCR4 is a transcriptionaltarget of SRC-3. Therefore, our study first identified that SRC-3 plays a critical role in the bladder cancer, whichmay be a target beneficial for its prevention and treatment.