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One of the most important causes of exfoliation glaucoma is the exfoliation syndrome in which lysyl oxidase-like 1 (LOXL1) gene most-strongly associated with exfoliation glaucoma. The rs2165241 was located in intron 1 of LOXL1 gene and it is believed that rs2165241 could alter LOXL1splicing. The objective of this comprehensive study was the association of rs2165241 single nucleotide polymorphisms (SNP) in patients with exfoliation glaucoma and control individuals. Sixty unrelated exfoliation glaucoma (XFG) on the Iranian’s patients, as well as 40 control subjects were studied for a LOXL1 gene polymorphism (rs2165241) by using PCR sequencing. According to the results of this study, there is significant associations between TT genotype of rs2165241 SNP and XFG (P<0.0001); the T allele for rs2165241 was more frequent in patients compared to control subjects (P<0.0001), and C allele was a factor of the utmost importance in modifying XFG. Thereby, patients with TT as well as TC genotypes had a high potential for XFG disease. The clinical data in case and control group showed that IOP in left and right (p= 0.019 and p=0.032, respectively) was significantly correlated with XFG. Consequently, the findings of this research declared the good agreement between the relationship of rs2165241 SNP and XFG disease in Iranian’s patients.