Drooling is both a clinical sign for the diminished control of saliva and oral motor function and a heavy social burden for patients. We report a case in which drooling deteriorated after radiotherapy of the head and neck region as the primary treatment for hypopharyngeal cancer, although radiotherapy of the salivary glands is known to be an effective treatment option for drooling. In this particular case, injection of botulinum toxin in the parotid and submandibular glands significantly reduced drooling. The excellent response to botulinum toxin is of great clinical interest for similar RT non-responders.