Background: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies worldwide, but there is lack of reliable clinical diagnostic biomarkers. We explored the clinical value and functions of Talin 2 (TLN2) in the progression of ccRCC.Methods: A bioinformatic analysis was performed to determine the clinical value of TLN2 in ccRCC.TLN2 expression was evaluated by immunohistochemistry (IHC), real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in ccRCC tissues and cells. The functions of TLN2 in ccRCC were investigated by both in vivo and in vitro studies. The functions of TLN2 in ccRCC cell proliferation was determined by CCK-8 assays and colony formation assays. Transwell assays and wound healing assays were performed to detect the effects of TLN2 on ccRCC cell invasion and migration abilities. Apoptosis assay and cell cycle analysis were used to determine the influence of TLN2 on ccRCC cell apoptosis and cell cycle.Results: TLN2 was downregulated in ccRCC tissues and cells. Clinically, TLN2 was confirmed to be an independent factor for ccRCC patient prognosis. Results of colony formation and CCK-8 assays showed that TLN2 overexpression inhibited ccRCC cell growth. Moreover, wound healing assays and transwell assays indicated that TLN2 overexpression inhibited ccRCC cell invasion and migration. In vivo assays also indicated that TLN2 played an important role in ccRCC cell growth and metastasis. TLN2 also inhibited cell cycle progression and promoted apoptosis of ccRCC cells. Mechanistically, TLN2 was confirmed to exert anti-ccRCC functions through Wnt/β-catenin signaling.Conclusions: TLN2 served as a tumor regulator of ccRCC via Wnt/β catenin signaling, suggesting that it could be a promising therapeutic and prognostic biomarker for ccRCC.