Background: Head and neck SCC is a common cancer related to various factors. IL-10, a pleiotropic cytokine produced by macrophages, T-helper-2 cells, and B lymphocytes, is thought to play a potential pathogenetic or therapeutic role in a number of human conditions, such as inflammation, autoimmunity and cancer. The present study was designed to evaluate the relation between tissue expression, serum and salivary levels of IL-10 in head and neck squamous cell carcinomas (HNSCCs) and their correlation with clinicopathologic features. Materials and Methods: Samples were collected from 30 patients with HNSCCs and 24 healthy volunteers. IHC analysis was used to examine the tissue expression and ELISA was employed to measure serum and salivary levels. Results: Our study showed tissue expression of IL-10 to be significantily higher in patients (P: 0.001), but there was no relation between tissue expression, serum and salivary levels of the marker (P>0.05). Also except for a positive correlation between tissue expression of IL-10 and stage (P: 0.044), there was no relation between this marker and clinicopathologic features. There was no correlation between serum and salivary levels in either patients or controls. Conclusions: It seems there is no correlation between level of IL-10 in serum and saliva and this marker in saliva and serum does not reflect tissue expression.