Background: Bladder cancer (BC) is the most common cancer of the urinary tract and invariably predicts a poor prognosis. In this study, we found a reliable gene signature and potential biomarker for predicting clinical prognosis. Methods: The gene expression profiles were obtained from the GEO database. By performing GEO2R analysis, numerous differentially expressed genes (DEGs) were found. Three different microarray datasets were integrated in order to more precisely identify up-expression genes. Functional analysis revealed that these genes were mainly involved in cell cycle, DNA replication and metabolic pathways. Results: Based on protein-protein interactome (PPI) networks that were identified in the current study and previous studies, we focused on KIF15 for further study. The results showed that KIF15 promotes BC cell proliferation via the MEK -ERK pathway, and Kaplan-Meier survival analysis revealed that KIF15 expression was an independent prognostic risk factor in BC patients. Conclusion: KIF15 may represent a promising prognostic biomarker and a potential therapeutic option for BC.