Polymerase I and transcript release factor (PTRF)/Cavin1 regulates RNA polymerase I during transcription and plays a critical role in endocytosis. Abnormal expressions of PTRF were detected in multiple cancers according to increasing research. PTRF has been showed to involve in the formation and secretion of exosomes and can be detected in the exosomes, which suggests that PTRF would be a potential biomarker for diagnosis of clear cell renal cell carcinoma (ccRCC) using urine samples. Approximately 50-90% of ccRCC cases suffered abnormal epidermal growth factor receptor (EGFR), which activates a variety of signaling pathways, including the mitogen-activated protein kinase/extracellular signal-regulated kinase and Phosphoinositide 3-Kinase/Akt pathway. According to bioinformatic analysis of gene expression arrays of kidney clear cell carcinoma from The Cancer Genome Atlas, we found SHC1 was significantly overexpressed in high-grade ccRCC and correlated to poor prognosis, and also SHC1 was annotated in extracellular matrix process, which was regulated by EGFR. Further studies showed that the expression of PTRF was regulated by SHC1 through EGFR-Phosphoinositide 3-Kinase/Akt pathway. PTRF was detected in the exosomes isolated from ccRCC patients' urine and ccRCC cancer cells culture medium. It suggested that the abnormal SHC1-increased PTRF, which is detected in exosomes from urine, would be a potential marker for ccRCC diagnose and treatment.