Introduction: Saliva has gained attention as an important diagnostic fluid because it contains biomolecules that have the potential to detect early-stage cancer or to monitor the response to treatment in patients. Several saliva-based proteins have been proposed as potential biomarkers for head and neck cancers (HNC). Areas covered: This review aims to provide an update on saliva-based protein biomarkers for HNC, often studied in observational research and clinical trials. Expert opinion: Despite the increasing number of studies relating to salivary proteins as biomarkers for HNC, there is no consensus regarding which proteins have the best clinical utility. Most studies have analyzed individual proteins and not a protein panel approach. It must be considered that combining different proteins as a panel can increase the accuracy and will have the potential to change the current clinical practice for HNC patients.