We examined EPB4.1L5 expression in urothelial cancer cells, T24 and UMUC-3 by western blotting and immunofluorescence staining. We found the EPB4.1L5 expressin in those cell lines.Retrospective analysis of the clinical records of 165 patients with UTUC (Ta-4N0M0) subjected to radical nephroureterectomy and immunohistochemical examination of EPB4.1L5 expression in those tissues. The score of EPB4.1L5 significantly correlated with tumor grade, pathological T stage, and lymphovascular invasion. The 5-year Kaplan-Meier recurrence-free survival and cancer-specific survival rates were 54.1% and 59.5% in patients with high EPB4.1L5 expression, compared with 81.6% and 87.2%,(all p＜0.001) in their counterparts. Multivariate analyses revealed that high expression of EPB4.1L5 was one of the independent prognostic factors for tumor recurrence and cancer specific survival.