Background/aim: We investigated the association of three IL-10 promoter single-nucleotide polymorphisms and altered IL-10 plasma levels with the risk of head and neck cancer (HNC). Materials and methods: Study subjects comprised 194 HNC patients [137 nasopharyngeal cancer (NPC) and 57 laryngeal cancer (LC)], and 263 healthy controls. Genotyping of rs1800896 (-1082A>G), rs1800871 (-819C>T), and rs1800872 (-592A>C) IL-10 variants was performed by real-time PCR; IL-10 levels were measured by enzyme amplified immuno sensitivity assay (EAISA). Results: Carriage of rs1800896 A/A genotype was more frequent in the HNC and NPC cases, but was less frequent in the controls than the LC patients. Significant differences in IL-10 levels were observed between the rs1800896A/G genotype-carrying NPC patients and the controls. Positive association with NPC and LC was observed for rs1800871C/C, and carriage of rs1800872A/A genotype, and A allele were associated with higher risk of HNC and NPC, but not LC. GT rs1800896-rs1800871 haplotype was more frequent among the HNC and NPC patients than the controls in contrast to GC haplotype, which has a protective effect. Positive association was found between TA haplotype and LC. Conclusion: Our results demonstrate that IL-10-1082, IL-10-819, and IL-10-592 variants, and haplotypes GC and GT constitute biomarkers for early detection of HNC, especially NPC subtype. IL-10 -819T/C and TA haplotype may be used as biomarkers for early detection of LC.