Head and neck cancer can be painful, debilitating, and refractory to oral medications. Due to the association of the sphenopalatine ganglion (SPG) with maxillary nerve sensory fibers, SPG blocks may be used to treat the pain of the hard and soft palate, tonsils, nasal cavity, paranasal sinuses, oral gingiva, premaxillary soft tissue, maxilla, and orbital floor. We present the first case series of performing SPG blocks utilizing TX360 nasal atomizers or angiocatheters to treat head and neck cancer-related pain. Pain scores were reduced by 38% to 80% with an average pain relief duration of 23 days.