<p>The ATP-binding cassette (ABC) transporter family is among the largest protein superfamilies, consisting of seven subfamilies, and plays an important role in various physiological processes and in the clinical manifestations of many diseases. The early clinical signs of head and neck cancer (HNC) are often subtle, resulting in most patients being diagnosed at more advanced stages. This late diagnosis adversely affects tumor treatment, and the resistance of certain tumors to chemotherapy further poses significant challenges for clinical management. Several previous studies have indicated a correlation between the ABC protein family and multidrug resistance (MDR) in tumors. This article offers a thorough review of the subfamilies, structures, functions, and roles of ABC transporters in MDR related to head and neck tumors, with the aim of providing insights and recommendations for overcoming MDR in this context.</p>