To examine the association between human leukocyte antigen (HLA) and nevirapine (NVP)- and efavirenz (EFV)- induced cutaneous adverse reactions in HIV patients, we conducted a case-control study at our center consisting of 96 patients. Patients were further assigned based on the occurrence of cutaneous adverse events and the drugs involoved. All patients were subjected to NGS-based screening with a focus on HLA phenotype, including the presence of HLA-B, HLA-C and HLA-DRB1. Our data indicated that the HLA-C*01:02:01 allele presence was observed in 47.4% (18/38) of patients in the EFV hypersensitive group compared with 18.9% (7/30) in the control group [odds ratio (OR) = 5.837; 95% confidence interval (CI) = 1.727 - 19.722, P = 0.005]. In contrast, the occurrence of HLA-DRB1*08:03 was found to be significantly lower in the EFV hypersensitive group (4/38, 10.5%) compared to the corresponding control group (12/37, 32.4%), [OR = 0.148; 95% CI = 0.035 - 0.625, P = 0.009]. In addition, the HLA-DRB1*04:05:01 antigen was expressed more frequently in the NVP hypersensitive group (23.8%, 5/21) compared to the control group (10.8%, 4/37) [OR = 7; 95% CI = 1.265 - 38.793, P = 0.026]. Our data not only revealed a significant association between HLA-C*01:02:01 and EFV-induced cutaneous adverse reactions but may also shed light on defining the treatment for Chinese HIV patients.