In this study, one hundred and three HIV-positive Chinese Han patients treated with a nevirapine (NVP)-based regimens were investigated for the association between nevirapine hypersensitivity reaction (NVP HSR) and human leukocyte antigen (HLA) allele. HLA-Cw, -DRB1 alleles were determined in 32 NVP HSR cases and 71 NVP-tolerant patients. We found that considerable overlap was observed for the clinical and demographic characteristics of the 32 hypersensitive patients and 71 tolerant patients. Twelve out of 32 NVP HSR cases developed allergic hepatotoxicity. More HLA-Cw*04 alleles were observed in NVP HSR cases than in NVP-tolerant cases (p=0.029). The frequency of HLA-DRB1*15 in NVP-tolerant cases was significant higher than that in NVP HSR cases ( p=0.018). Multivariate logistic regression identified that HLA-Cw*04 presence was a risk factor related to NVP HSR (p=0.030, OR=3.611, 95% CI of OR: 1.135-11.489). To clearly understanding its value in clinical practice, further studies involving larger cohorts of patients from different races with different levels of immune suppression are needed.