Alterations in microRNA (miRNA) expression have been shown to be involved in the tumor response to chemotherapy. However, the possible role of miR‑101 in cisplatin sensitivity in human bladder cancer cells remains unclear. In this study, quantitative polymerase chain reaction and western blotting were utilized to determine the expression profiles of miR‑101 and cyclooxygenase‑2 (COX‑2) in human bladder cancer cells. The effect of miR‑101 and small interfering RNA (siRNA) against COX‑2 on cell viability was evaluated using MTT assays, and apoptosis levels were determined using fluorescence‑activated cell sorting analysis of Annexin V/propidium iodide‑stained cells. Luciferase reporter plasmids were constructed to confirm direct targeting. This study found that the expression of miR‑101 was downregulated in the cisplatin‑resistant cell line T24/CDDP as compared with that in the parental line, T24. Furthermore, overexpression of miR‑101 significantly increased the anti‑proliferative effects and apoptosis induced by cisplatin, whereas knockdown of miR‑101 significantly decreased the anti‑proliferative effects and apoptosis induced by cisplatin. In addition, downregulation of miR‑101 induced cell survival and cisplatin resistance through the upregulation of COX‑2 expression. Luciferase gene reporter assays confirmed that COX‑2 was a direct target gene of miR‑101. Inhibition of COX‑2 using COX‑2 siRNA abrogated the cisplatin resistance induced by miR‑101 downregulation. These results suggest that miR‑101 may provide a novel mechanism for understanding cisplatin resistance in bladder cancer by modulating the COX‑2 pathway.