Abstract: OBJECTIVE To investigate the effect and mechanism of DNA methyltransferase inhibitor decitabine on the invasion and migration ability of renal cancer cells 786-O and 769-P. METHODS The miR-200c/141 expression levels in renal cell carcinoma and its adjacent tissues were detected by RT-qPCR. MiR-200c/141 were induced by 2.5 μmol·L^-1 decitabine and detected by RT-qPCR. Transwell assay and scratch assay were used to detect the effect of decitabine, miR-200c/141 on cell invasion and migration respectively. The mRNA and protein levels of E-cadherin were detected by RT-qPCR and western blot. RESULTS Compared with adjacent tissues, miR-200c/141 were significantly down regulated in renal cell carcinoma. The expression of miR-200c/141 could be induced in the 786-O and 769-P cells after treated with 2.5 μmol·L^-1 decitabine. Scratch assay and Transwell assay results showed that decitabine, miR-200c/141 could inhibit cell migration and invasion. The expression of E-cadherin was upregulated in 786-O and 769-P cells after treated with decitabine, which associated with epithelial mesenchymal transition. CONCLUSION Decitabine can weaken the migration and invasion ability of 786-O and 769-P cells by up-regulating the expression of miR-200c/141.