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Introduction:The present study aimed to assess human leukocyte antigen (HLA) typing differences between smokers with Reinke’s edema and those with laryngeal squamous cell carcinoma (SCC). Materials and Methods:The HLA class I, II alleles were examined in 76 unrelated Iranian patients using low-resolution polymerase chain reaction with the sequence-specific primer (PCR-SSP) method. Results:The frequency of the HLA-A*36 allele and HLA-B*35 was significantly higher in patients with SCC. The frequency of HLA-DRB1*01 alleles in Reinke’s edema was significantly higher, as compared to that in others. In the volunteer group, HLA-DRB1*13 and HLA-DRB1*15 were significantly higher. Conclusions:As evidenced by the obtained results, HLA-A*36 was significantly higher in SCC, as compared to that in volunteers and Reinke’s edema patients. It can be concluded that being positive for HLA-A*36 increases the chance of SCC by three times. This result should be further investigated in cohort studies conducted on larger samples. Furthermore, HLA-A*24 was significantly higher in the volunteer group, as compared to that in other groups. The HLADRB1*01 was remarkably higher in Reinke’s edema, as compared to that in SCC.