MicroRNAs (miRNAs) are important regulators involved in various cancers, including renal cell carcinoma (RCC). The role of the miRNAs involved in RCC progress and metastasis is largely unknown. Here, miRNA microarray analysis was performed to screen the significant miRNAs involved in RCC progress, and miR-144-3p was chosen for further study. We found that the expression of miR-144-3p was significantly lower in RCC specimens and cell lines. In addition, low expression level of miR-144-3p is correlated with tumor progression and poor survival in RCC patients. Based on in vitro assays, we found that miR-144-3p significantly inhibit cancer cell proliferation and progression. Furthermore, function studies revealed that miR-144-3p was significantly correlated with the metastasis potential by affecting the epithelial-mesenchymal transition (EMT). Moreover, Mitogen-activated protein kinase 8 (MAP3K8) is direct target of miR-144-3p, while the expression levels of MAP3K8 were inversely correlated with the expression levels of miR-144-3p in RCC tissues. Overall, our findings demonstrate that miR-144-3p targeted the MAP3K8 pathway to reduce tumor cells proliferation and metastasis in RCC, suggesting that this axis may provide a novel therapeutic target for RCC therapy. (C) 2016 Elsevier Inc. All rights reserved.