The HLA system is the main system of tissue matching in humans. The genes of the HLA system are located on the shorter arm of chromosome 6 and are divided into three classes: I, II, III. The analysis of HLA genes is extremely important in organ transplantation and transfusion treatment, forensic medicine, population research, population migration studies and the diagnosis of certain autoimmune diseases. The main characteristics of the HLA system are polymorphism, genetic imbalance of association, irregular tissue representation, crossing-over, cross-reactivity, proper segregation and racial and population specificity. Serological and molecular testing are used to determine HLA antigens and genes, and the choice of method depends on laboratory needs. Standard method of serological testing is the microlymphocytotoxicity test, and the molecular methods used are PCR-SSO (Polymerase chain reaction-Sequence Specific Oligonucleotides) and PCR-SSP (Polymerase chain reaction-Sequence Specific Primer). The goal of the paper was to point out the connection of the HLA system with autoimmune diseases by reviewing and analyzing a large number of scientific papers and the importance of HLA locus allele frequency in patients with celiac disease, Hashimoto’s thyroiditis, rheumatoid arthritis and type 1 diabetes as a diagnostic parameter. Autoimmune diseases are a group of complex diseases that occur as a result of the impossibility of the immune system to distinguish between self and nonself. The main characteristic of these diseases is the production of reactive T and B lymphocytes and autoantibodies. Autoimmune diseases are organ-specific and non organ-specific. HLA typing is of great use because it provides additional insights into the diagnosis and treatment of autoimmune diseases. The association of numerous antigens and alleles of the HLA system with autoimmune diseases has been proven.