Extracellular vesicles (EVs) directly isolated from surgically resected ccRCC tissues and adjacent normal renal tissues were analyzed with quantitative LC/MS. This analysis identified 3,871 tissue‐exudative EV proteins, among which azurocidin (AZU1) was highly enriched in tumor EVs (fold‐change = 31.59).AZU1 content in EVs was significantly higher in ccRCC patients compared to those from healthy donors.Subsequent functional analyses indicated that EV‐AZU1 could be engaged with vesicle‐mediated hematogenous metastasis of RCC. Here, AZU1 is linked to renal cell carcinoma.