This study investigated whether killer-cell immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA)-C alleles, receptors and ligands of natural killer cells are associated with the development of human papillomavirus (HPV)-related cervical disease in Korean women. Blood samples from 132 women with HPV-related cervical disease and 159 women without HPV infection were collected for genotyping of KIR genes and HLA-C alleles. Although no relationship was found between KIR genes and HPV-related cervical disease, a significant relationship was found between HLA-C alleles as ligands of KIR and HPV-related cervical disease. Women with HPV-related cervical disease were found to be significantly more likely to carry HLA-C*0303, particularly those with HPV 16 or 18 infection, and less likely to carry HLA-C*01 compared to women without HPV infection. HLA-C*0303 was found to confer susceptibility to HPV-related cervical disease, whereas HLA-C*01 was found to confer a protective effect against HPV-related cervical disease.