Hydatid disease (HD) is a parasitosis caused by Echinococcus granulosus, which is still an important health problem worldwide, and our country is an endemic region for HD. There is little information regarding the role of human leucocyte antigen (HLA) in genetic susceptibility or resistance to HD. In this study, we aimed to investigate the HLA profile of Turkish children with HD and to compare them with healthy individuals. We also planned to investigate whether HLAs have a potential role in the predisposition to or prevention of the occurrence of HD and to study the relationship between the clinical features of HD and the HLA profile of the patients. The study included 81 children (25 boys, 56 girls) with HD aged between 3 and 18 years. All the patients' and control subjects' HLA class I and II antigens were examined, antigen allele frequencies were calculated, and clinical characteristics were also evaluated. The frequency of HLA-B18, -DR1, and -DR15 alleles were significantly different between the patients and healthy groups; HLA-DR15 antigen might be associated with HD occurrence, and the presence of HLA-B18 and HLA-DR1 antigens might be associated with HD resistance. Compared with the healthy group, patients with lung HD had a significant increase in HLA-B44 frequency, and liver HD patients had a significant increase in HLA-DR15 antigen frequency. Furthermore, presence of HLA-DR11 was found to be a significant factor associated with cure of the disease. We concluded that HLA types have significant impact on the development of HD and clinical course of disease.