Abstract: Objective To explore the effects of Trim21 knockdown and over-expression on the proliferation, migration and invasion of renal carcinoma cells and related mechanism. Methods The relationship between Trim21 expression and the prognosis of renal carcinoma patients were analyzed by TCGA database. The baseline expression of Trim21 in renal carcinoma cells lines HK2, 786-O, ACHN and Ketr3 was analyzed by Western blot. After Trim21 knockdown and over-expression, the knockdown and over-expression efficiency was verified by Western blot. The cell proliferation was detected by CCK8 assay. The cell migration and invasion abilities were detected by wound-healing assay and Transwell assay, respectively. Western blot was used to detect the level of epithelial-mesenchymal transition (EMT) associated protein. Results According to TCGA analysis, patients with low expression of Trim21 showed shorter survival. Based on Western blot results, the expression of Trim21 was detected in different renal carcinoma cell lines. Trim21 knockdown promoted the proliferation, migration and invasion in renal carcinoma cells. In contrast, Trim 21 over-expression inhibited the proliferation, migration and invasion in renal carcinoma cells. Furthermore, Trim21 knockdown down-regulated the expression of E-cadherin, but up-regulated N-cadherin and Vimentin. In contrast, Trim 21 over-expression resulted in increased levels of E-cadherin and decreased levels of N-cadherin and Vimentin. Conclusions Trim21 suppresses the proliferation of renal carcinoma cells and inhibits migration and invasion abilities of renal carcinoma cells through regulating the expression of EMT-related proteins.