BACKGROUND Leukemia is common in aging adults and has very high mortality worldwide. The present study was designed to investigate the therapeutic efficacy of miR-18a inhibitor against WEHI-3 and THP-1 leukemia cells. MATERIAL AND METHODS The changes in miR-18a inhibitor-transfected WEHI-3 and THP-1 cell proliferative potential was measured by use of the Cell Counting Kit-8 assay. Apoptotic changes were analyzed by electron microscopy, and evaluation of PI3K, AKT, mTOR, and PTEN expression was assessed by RT-qPCR assay. RESULTS Transfection of miR-18a inhibitor significantly (P<0.05) suppressed the proliferative potential of WEHI-3 and THP-1 cells. The WEHI-3 cells showed the presence of characteristic apoptotic bodies on transfection with miR-18a inhibitor at 48 h. Flow cytometry showed that miR-18a inhibitor transfection significantly (P<0.05) increased the WEHI-3 cell percentage in G1 phase. The transfection of miR-18a inhibitor significantly (P<0.05) promoted apoptosis in WEHI-3 cells. In WEHI-3 cells, miR-18a inhibitor transfection markedly suppressed the expression of PI3K, AKT, and mTOR mRNA. The expression of PTEN mRNA was significantly (P<0.05) upregulated by miR-18a inhibitor transfection in WEHI-3 cells. CONCLUSIONS The present study investigated the therapeutic efficacy of miR-18a inhibitor against WEHI-3 and THP1 leukemia cells. The study demonstrated that miR-18a inhibitor suppressed the proliferative potential of WEHI-3 and THP1 cells and activated apoptotic process through upregulation of PTEN mRNA expression. Therefore, miR-18a inhibitor can be of therapeutic importance for the treatment of leukemia.