Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease of the hair follicle typically presenting recurrent, painful, and inflamed lesions on the inverse areas of the body. Although its pathogenesis remains unknown, the immune system appears to play a potential role. To date, two previous studies have not found any association between the Human Leukocyte Antigen system (HLA) and HS. In this study we analyzed the HLA-A , -B, -C ; and DRB1 , - DQA1, and –DQB1 allele distribution in 106 HS patients and 262 healthy controls from a Caucasian population in Cantabria (northern Spain). HLA-A *29 and B *50 were significantly more common in HS patients and A *30 and B *37 in controls, but these associations disappeared after statistical correction. DRB1 *07, DQA1 *02, and DQB1 *02 were significantly more common in controls ( p 0.026, p 0.0012, and p 0.0005, respectively) and the HLA allele DQB1 *03:01 was significantly more common in HS patients ( p 0.00007) after the Bonferroni correction. The DRB1*07~DQA1*02~DQB1*02 haplotype was significantly more common in controls ( p < 0.0005). This is the first study showing an association between HLA-class II and HS. Our results suggest that HLA-II alleles ( DRB1 *07, DQA1 *02, DQB1 *02, and DQB1 *03:01) and the DRB1 *07~ DQA1 *02~ DQB1 *02 haplotype could influence resistance or susceptibility to HS.