Tumours of the head and neck induce severe pain in patients, compromising their quality of life and impeding basic life functions. Treating this pain with currently available methods poses a significant therapeutic challenge. Current efforts are focused on identifying solutions that directly target the mechanisms responsible for the pain. However, the precise molecular mechanisms underlying the development of this phenomenon are not fully understood. Among the pain-inducing factors in head and neck cancer, cytokines play a crucial role. These include TNF-, interleukins, endothelin, and neurotrophic factors such as NGF. Secreted by the tumour and surrounding tissue, these substances activate and sensitise receptors on afferent neurons. Receptors for these molecules belong to the TRP family and their specific receptors. Additionally, the microenvironment of the tumour, comprising elements like proteases and hydrogen ions, contributes to pain through the activation and regulation of other pain receptors, particularly those in the PAR family. This article presents the current state of knowledge regarding the most widely studied pathomechanisms involved in the development of pain in head and neck tumours.