The aim of our study was to analyse a significance of tumour necrosis factor (TNF)‐α promoter gene polymorphisms in relation to the HLA‐DR locus in genetic predisposition to pemphigus. TNF‐α gene polymorphisms in position ‐238 and ‐308 were identified using a modified polymerase chain reaction‐restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus) and 87 healthy controls. The HLA‐DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls.Carriers of the TNF‐α polymorphic ‐308 A allele were found to be more frequent in the pemphigus foliaceus group in comparison with the control group (odds ratio (OR)=8.12; P = 0.0005). A significant association between HLA‐DRB1*04 (OR=3.86; Pcor = 0.0001) and DRB1*14 (OR=8.4; Pcor = 0.0001) and pemphigus vulgaris was found. In this group of patients a decreased frequency of HLA‐DRB1*07 (OR=0.08; Pcor = 0.006) was also identified.We have shown for the first time a positive association of TNF‐α polymorphism in position ‐308 with pemphigus foliaceus.