Abstract  Objective To investigate the mechanism of anti-apoptosis effect of miR-21 in renal cell carcinoma. Methods  Human Renal cancer carcinoma cell lines Caki-1 and OS-RC-2 were transfected with As-miR-21 or non-special oligonucleotides (as negative control) or nothing (as blank control).Cell apoptosis was detected by using AnnexinV FITC Apoptosis Dectecting Kit. After reduction of miR-21, Fas ligand and metalloproteinase inhibitor 3 (TIMP3) expression and luciferase activity were detected by Western blot and luciferase reporter assay. The effect of TIMP3 on miR-21-induced anti-apoptosis was determined by transfection with TIMP3 lacking 3’ untranslatedm region and miR-21. Results   The reduction of miR-21 by antisense oligonucleotides induced cell apoptosis by activation of caspase pathway in renal cell carcinoma cells. Moreover, bioinformatics analysis revealed that miR-21 has the potential to regulate multiple poptosis-related genes. The reduction of miR-21 inhibited Fas ligand and TIMP3 expression by targeting the binding site within the 3’ untranslated region. Finally, the introduction of TIMP3 cDNA without 3’ untranslated region abrogated miR-21-induced anti-apoptosis. Conclusions  MiR-21 can increase cell anti-apoptosis in renal cancer through FASL and TIMP3 pathways.