MicroRNA (miR)-21 has many regulatory functions in the cell, including activities in cancer cells and cancer stem cells. Large tumor suppressor gene 1 (LATS1) is a target of miR-21 that could mediate several of these phenotypes. This study explored the effect of miR-21 silencing in renal cancer cell function and LATS1 expression. Silencing of miR-21 in Caki-2 cells reached an efficiency of 55-60%. This was sufficient to detect decrease in Caki-2 cell proliferation and migration invasion capacity. miR-21 silencing increased LATS1 expression at both mRNA and protein levels. The number of tumor spheres formed by cells expressing si-miR-21 was significantly reduced and the expression of tumor stem cell markers Nanog and CT3/ 4 were significantly downregulated. miR-21 seems to regulate LATS1 expression in renal cancer Caki-2 cells, resulting in reduced proliferation, invasion, and cancer stem cell phenotype. miR-21 may promote malignant phenotype of tumor cells through LATS1 silencing, which can be regarded as a new target candidate gene for renal cancer treatment.