Abstract: Objective  To investigate biomarkers Ki-67 and P53 expression in primary upper tract urothelial carcinoma tissues. Combined with conventional cliniopathological parameters, we analysis their correlation with bladder tumor recurrence in patients with primary upper tract urothelial carcinomas after radical nephroureterectomy. Methods The data was retrospectively collected in 115 patients of primary upper tract urothelial carcinomas. The expression of tumor markers Ki-67 and P53 protein were detected by immunohistochemistry. Combined with traditional cliniopathological factors and biomarkers, we explore risk factors of bladder tumor recurrence. Results Normal Ki-67 expression rate was 44.87% (48/107), and Ki-67 over-expression rate was 55.13% (59/107). P53 negative expression rate was 34.86% (38/109), mild positive rate was 25.69% (28/109), positive rate was 17.43% (19/109), and strong positive rate was 22.02% (24/109). Ki-67 and P53 expression were both associated with tumor grade (P = 0.003). The incidence of bladder cancer was 11.30% (13/115) in patients with the primary upper tract urothelial carcinomas after radical nephroureterectomy, and the mean follow-up time was 48.50 months (7-130 months). Multivariate survival analysis revealed that more than 65 years (P = 0.040), ureteral tumors (P = 0.008) and the low expression of Ki-67 (P = 0.041) were independent predictors for bladder cancer. Conclusion Normal Ki-67 expression was an independent predictor for bladder tumor recurrence in primary upper tract urothelial carcinomas after radical nephroureterectomy.