Brachytherapy is a type of radiation therapy in which the radioactive source is directly delivered to the tumor and is used to treat a variety of malignancies. Although the local control effect of brachytherapy is higher than that of external beam radiation therapy (EBRT), it is often the case that brachytherapy is more invasive than conventional EBRT. As a result, patients receiving head and neck brachytherapy confront several physical, nutritional, and pain management issues. The nurses caring for patients with head and neck cancer receiving high-dose rate interstitial brachytherapy (ISBT) should have a thorough understanding of radiation therapy principles, technology, applicator management, and the acute and chronic side effects of ISBT. However, there are no appropriate textbooks or review articles regarding nursing care for head and neck patients undergoing ISBT. The purpose of this article is to provide radiation oncologists and nurses who want to start head and neck ISBT with a comprehensive guide regarding nursing care and to help the wide spread of this treatment strategy.