Polypyrimidine tract-binding protein 1 (PTBP1), a heterogeneous nuclear ribonucleoprotein, is a multi-functional RNA-binding protein. PTBP1 participates in a number of biological processes, including maintaining cell structure and motility, immunity, protein metabolism and the cell cycle. The present study aimed to investigate the association between PTBP1 expression and the prognosis and clinicopathological characteristics of patients with renal cell cancer (RCC). The potential mechanism of action of PTBP1 in the metastasis of RCC was also investigated. The results demonstrated that PTBP1 was overexpressed in RCC tissues compared with normal renal tissues. Furthermore, PTBP1 expression was negatively associated with patient prognosis and positively associated with tumor size, pathological tumor (pT) and pathological metastasis (pM) status and tumor lymph node metastasis (TNM) stage. PTBP1 knockdown in vitro inhibited RCC cell migration, invasion, proliferation and angiogenesis, and it was demonstrated that PTBP1 affected RCC cells primarily via the hypoxia inducible factor-1α pathway. Furthermore, PTBP1 knockdown decreased RCC lung metastasis in vivo. The present study demonstrated that PTBP1 knockdown suppresses tumor progression and metastasis, indicating that PTBP1 is an important prognostic factor in RCC and that it may be developed as a novel method of treating patients with RCC.