Our recently study had showed that miR-137 could inhibit renal cell carcinoma (RCC) growth in vitro and in vivo, and function as tumor suppressor in RCC. However, the mechanism leading to suppressive effect of the miR-137 remains largely unclear in RCC due to lack of molecular target information. In this study, we investigated underlying molecular mechanism of miR-137 regulating invasion and migration in CRC cells. It was found that miR-137 over-express significantly in cell migration and invasion of RCC cells. A bioinformatics analysis identified a putative miR-137 binding site within the 3"-UTR of PIK3R3. Luciferase reporter assay revealed that PIK3R3 was a direct target of miR-137 in RCC cells. Quantitative RT-PCR and western blot assay showed that overexpression of miR-137 could decrease the expression of PIK3R3 on mRNA level and protein level. Importantly, we found that downregulation of PIK3R3 by siRNA performed similar effects with miR-154 overexpression on NSCLC cells in migration and invasion, while overexpression of PIK3R3 in RCC cells attenuated the suppressive effects of miR-137 on cell migration and invasion. Taken together, these results showed that miR-137 inhibited migration and invasion of RCC cells by repressing PIK3R3 expression, suggesting that miR-137 might be a novel target for the treatment of RCC.