Renal clear cell carcinoma (ccRCC) is considered to be the most common renal cell carcinoma. Molecular targeted therapy and immunotherapy improve the prognosis of patients with advanced RCC, but recurrence, progression of distant metastasis, and side effects are still important issues related to these treatments. Syndecans is a multi-functional family including four cell surface molecule members, which has various biological functions. Syndecan-3 (SDC3) is the largest one, which not only can affect a variety of physiological functions but also affect the progression of many cancers. However, its expression in renal cell carcinoma and its possible role in the progression and metastasis of renal cell carcinoma is not clear. According to the TCGA database and IHC analysis, the mRNA and protein levels of SDC3 were significantly increased in ccRCC tissues were found. The expression of SDC3 was associated with the prognosis of patients with renal cell carcinoma and with the tumor size of the patients was found. Further research indicated that SDC3 knockdown inhibits the proliferation of ccRCC cell lines. In summary, our study demonstrated high expression of SDC3 promotes ccRCC cell malignancy and sheds light on developing novel therapeutic approaches based on SDC3.