The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors occurringin the head and neck. Tumor necrosis factor related apoptosis induce ligand (TRAIL) and TRAIL-receptors(DR4, DR5, DcR1, DcR2) are known as important members of TRAIL-mediated biochemical signaling pathway.Associations between polymorphisms in these genes and clinicopathological characteristics of human laryngealcarcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAILand TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patientswith laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/Tgenotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)analysis and sTRAIL levels were measured by ELISA. There were significant differences in the distribution ofDR4 C626G genotypes and frequencies of the alleles between laryngeal cancer patients and controls (p<0.001)but not in TRAIL 1595 C/T. We found the increased frequency of the DR4 C626G homozygote CC genotypein patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significantrelationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels inthe laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patientswith early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might beassociated with progression of laryngeal cancer in the Turkish population.