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Purpose: The extracellular matrix (ECM) is reported to play an important role in tumorigenesis and progression.Collagen VI is a major ECM protein.In this study, we investigated the potential role of the COL6A1 gene, which encodes the α 1 polypeptide of collagen VI, in the biological functions involved in the progression and outcome of clear cell renal cell carcinoma (ccRCC).Materials and methods: A total of 288 ccRCC patients who underwent radical nephrectomy (RN) or nephron sparing nephrectomy (NSS) at Fudan University Shanghai Cancer Center (FUSCC) were enrolled.Total RNA was extracted from frozen samples obtained from the tissue bank of FUSCC and expression of COL6A1 was determined by qRT-PCR.The clinical relationship between COL6A1 expression and ccRCCprognosis was analyzed.These data were then validated in the Cancer Genome Atlas (TCGA) cohort.We also investigated the effect of COL6A1 overexpression in a xenografted tumor model in nude mice in vivo.Results:In multivariate analysis of TCGA cohorts, COL6A1 high expression was predictive of poor prognosis in ccRCC patients' overall survival (OS)(HR: 2.588 95%CI 1.616-4.146)and disease free survival(DFS)(HR:3.106 95%CI 1.534-6.288).In FUSCC cohorts, after adjusted for relevant factors, the COL6A1 expression indicates poor prognosis in ccRCC patients' s OS (HR2.211;95% CI, 1.360-8.060) and DFS (HR 3.052;95%CI, 1.500-6.210).COL6A1 overexpression promoted tumor growth in xenograftednude mice.Conclusion: Increased COL6A1 expression correlateswith poor prognosis inccRCC patients.Moreover,COL6A1 stimulates tumor growth in vivo.