Background: Hepatic hydatid disease (HHD) is a parasitic zoonosis caused by larval stage of Echinococcus tape worm. In addition to environmental factors, genetic constitution of hosts seems to play a crucial role in acquiring the infection and developing disease. Aims: This study was carried out to investigate the association of HLA-class I and class II (A, B, DR and DQ) alleles with HHD by genotyping in Iraqi patients, as well as to provide information about genotypes that confer susceptibility or resistance to develop the disease. Materials and Methods: Twenty patients with HHD, their age range (20-50) years and 20 healthy controls their ages were matched with the patients were enrolled in this study. Blood was collected from patients and controls, DNA was extracted from blood samples, and then HLA-class I and class II genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSO). Results: The present findings showed that frequencies of HLA-A*32 (65%; P=0.011), DRB1*11 (60%; P=0.004) and DQB1*03 (70%; P=0.007) alleles are significantly higher in patients than controls, while the frequency of DRB1*04 was significantly decreased in patients when compared to controls (25% vs. 75%; P=0.002). Furthermore, the current study could not observe significant differences in the frequencies of HLA-B alleles between patients and controls. Conclusions: We concluded that HLA-A*32, DRB1*11 and DQB1*03 alleles might contribute to the increased susceptibility to HHD and DRB1*04 could be a protective marker against the disease.