Update publication information. Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Only limited data are available concerning potential noninvasive biomarkers for disease monitoring. Here, we investigated the proteomic profile of plasma in 362 UTUC patients and 239 healthy control samples. The results show 520 elevated proteins in UTUC patients are mainly involved in acute-phase response and tRNA aminoacylation pathways; while 317 descend proteins are enriched in sulfur metabolism and deubiquitination. We presented an integrated tissue-plasma proteomic approach to infer the highly specific tumor biomarkers for identify patients with muscle-invasive UTUC. We provided a protein panel that reflected lymph node metastasis, which is of interest to identify high risk and poor prognosis UTUC patients. We also identified a ten-gene signature and establishment of a prognostic nomogram predicting progression-free survival of UTUC. Finally, we further validated the biomarkers by parallel reaction monitoring (PRM) assay in a new independent cohort.