AIM: To evaluate the relationship between gene polymorphism (BclI, ER22/23EK, N363S) and the occurrence, progression and sensitivity to glucocorticoid of lacrimal gland benign lymphoepithelial lesion (LGBLEL). METHODS: Clinical peripheral blood samples of 52 LGBLEL patients and 10 normal volunteers were collected for DNA extraction and polymerase chain reaction sequencing to analyze single nucleotide polymorphism (SNP) genotypes. The lacrimal tissues of LGBLEL were surgically removed and made into paraffin sections for subsequent hematoxylin-eosin (HE) and Masson staining analysis. The duration of disease and hormone use of LGBLEL patients from diagnosis to surgery were also analyzed. The Meta-analysis follows PRISMA guidelines to conducted a systematic review of human studies investigating the relationship between the NR3C1 BclI polymorphism and glucocorticoids (GCs) sensitivity. RESULTS: There was no association between ER22/23EK or N363S and the occurrence of LGBLEL or GCs sensitivity (P>0.05); BclI GC genotype was closely related to GCs resistance (P=0.03) as is the minor allele C (P=0.0017). The HE staining and Masson staining showed that the GC genotype of BclI remarkably slowed down the disease progression and reduced fibrosis (P<0.05), especially for GCs-dependent patients (P<0.0001). Meta-analysis showed that BclI was not significantly associated with GCs responsiveness. CONCLUSION: The LGBLEL patients who carry the NR3C1 BclI allele C may be more sensitive to GCs and associated with lower fibrosis and slower disease progression. The results may guide the clinical treatment strategy for the LGBLEL patients.