Multidrug resistance (MDR) is a major impediment to cancer therapy. MG‑132 has been identified to be effective against MDR in several types of cancer. However, the mechanism of MG‑132 in head and neck squamous cell carcinomas remains unknown. Based on our previous study, the present detected P‑gp and P‑gp expression in hypopharyngeal carcinoma FaDu cells, revealing that their expression was lower than that observed in the MDR cell line FaDu/T. To reverse the MDR of FaDu/T cells, the present study introduced MG‑132 and demonstrated that the high expression of P‑gp/P‑gp in FaDu/T cells was attenuated in a time‑dependent manner. MG‑132 also strengthened the sensitivity of FaDu/T cells to multidrugs. c‑Jun N‑terminal kinase (JNK) activation was further observed in FaDu/T cells. However, P‑gp/P‑gp did not decrease when FaDu/T cells were pretreated with SP600125. These results indicated that MG‑132 reversed the MDR of hypopharyngeal carcinoma by downregulating P‑gp/P‑gp, and the underlying mechanism may be associated with the activation the of the JNK signaling pathway.