Glioma is among the most common types of cancer of the central nervous system and is difficult to cure. Due to the lack of glioma-specific treatments, patients with glioma exhibit high mortality rates. MicroRNAs (miRNAs) participate in the pathogenesis of glioma, and upregulation of specific miRNAs promotes cell proliferation, whereas apoptosis‑inducing miRNAs are markedly downregulated in the context of glioma. Therefore, miRNAs may be important contributors to the pathogenesis of glioma. In the present study, nine miRNAs were investigated as miRNA‑miRNA pairs, and the measured cell viabilities were consistent with the results of synergy predictions. Extensive synergy occurred among upregulated miRNAs in U87 cells, whereas downregulated miRNAs rarely exhibited synergism. Treatment with an miRNA‑miRNA pair exhibiting strong synergy increased the inhibitory effects of these miRNAs on tumor cells, and the combined inhibitory effects were increased compared with the sum of the individual inhibitory effects of each miRNA. Using cell viability assays, TUNEL staining, and flow cytometry, the present study demonstrates that cotransfection with miR‑20a and miR‑21inhibitors resulted in the highest synergistic effect on the promotion of apoptosis in U87 cells. The results of the present study provide important insights into the potential use of miRNAs in the treatment of glioma.