Head and neck cancer (HNC), which includes epithelial malignancies of the upper aerodigestive tract (oral cavity, oropharynx, pharynx, hypopharynx, larynx, and thyroid), are slowly but consistently increasing, while the overall survival rate remains unsatisfactory. Because of the multifunctional anatomical intricacies of the head and neck, disease progression and therapy-related side effects often severely affect the patient's appearance and self-image, as well as their ability to breathe, speak, and swallow. Patients with HNC require a multidisciplinary approach involving surgery, radiation therapy, and chemotherapeutics. Chemotherapy is an important part of the comprehensive treatment of tumors, especially advanced HNC, but drug resistance is the main cause of poor clinical efficacy. The most important determinant of this phenomenon is still largely unknown. Recent studies have shown that non-coding RNAs have a crucial role in HNC drug resistance. In addition, they can serve as biomarkers in the diagnosis, treatment, and prognosis of HNCs. In this review, we summarize the relationship between non-coding RNAs and drug resistance of HNC, and discuss their potential clinical application in overcoming HNC chemoresistance.