Multidrug resistance (MDR) is a major clinical obstacle in the successful treatment of patients with metastatic nasopharyngeal carcinoma (NPC). Results from previous studies suggest that microRNAs (miRNA) may be involved in promoting MDR in multiple cancer types. However, the role of miR-125b in modulating the MDR of NPC is elusive. In the present study, miR-125b expression in cisplatin (DDP)-resistant CNE2 cells (CNE2/DDP) was compared with parental counterparts, using reverse transcription-quantitative polymerase chain reaction. A >3-fold reduction in miR-125b expression levels was observed in CNE2/DDP cells compared with parental CNE2 cells. Ectopic expression of miR-125b by transfecting CNE2/DDP cells with miR-125b mimics, increased DDP-induced cytotoxicity, apoptosis and chemosensitivity. By contrast, suppression of miR-125b by transfecting CNE2 cells with miR-125b inhibitors, reduced DDP-induced cytotoxicity and apoptosis, and facilitated cisplatin resistance. The results suggest that miR-125b may regulate the sensitivity of NPC cells to DDP by modulating the expression levels of antiapoptotic factor B-cell CLL/lymphoma 2. Collectively, the results of the present study highlight miR-125b as a potential therapeutic target for reversing MDR in NPC.