Abstract: Objective To understand the relationship between human leukocyte antigen antigen-G (HLA-G)14 bp insertion/deletion polymorphism and the risk of herpes simplex encephalitis(HSE). Methods Polymerase chain reaction was performed to detect the HLA-G 14 bp insertion/deletion polymorphism of HSE patients and healthy controls and analyze the relationship between genotype and allele of HLA-G and risk of HSE. Results There was a significant difference in the distribution of HLA-G 14 bp genotypes between HSE patients and healthy controls(P=0.007). A significant increased frequency of HLA-G 14 bp del/del(59.13% vs. 41.04%, OR=5.56, P=0.018)was observed in HSE patients compared with the healthy controls, and the allele frequency of 14 bp deletion in HSE group outweighed that of control group(78.70% vs. 67.16%), the difference was statistical significant(OR=1.81, P=0.004). Conclusion HLA-G 14 bp insertion/deletion polymorphism might be related with HSE, and 14 bp deletion could be one of the risk genetic factors contributing to HSE.