The present study assessed the expression profiles of numerous microRNAs (miRs; miR-141, miR-187, miR-206, miR-218, miR-335 and miR-204) in 25 pairs of renal cell carcinoma (RCC) tissue samples and adjacent non-cancerous tissue. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis revealed that miR‑218 was significantly downregulated in RCC tissue samples. Next, web‑based algorithms were used to identify B‑cell lymphoma (BCL)9 as a possible target of miR‑218, which was confirmed by a subsequent luciferase assay. Furthermore, the mRNA expression of BCL9 in the tumor and adjacent normal tissue samples was assessed, and BCL9 was markedly upregulated in the tumor tissue samples compared with the adjacent non‑cancerous controls. In addition, miR‑218 mimics or its inhibitors were transfected into renal cell carcinoma cells and harvested 48 h later. RT‑qPCR and western blotting revealed that both the mRNA and protein expression levels of BCL9 were significantly downregulated by the miR‑218 mimics. However, inhibition of miR‑218 upregulated the expression levels of BCL9. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assay revealed that cell proliferation was suppressed in miR‑218 mimic‑transfected RCC cells compared with control cells; however, cell proliferation was significantly promoted in the RCC cells transfected with miR‑218 inhibitors compared with the controls. Taken together, it was demonstrated that miR‑218 modulated a novel molecular target and the present study provided novel insights into potential mechanisms of RCC oncogenesis.