Psoriasis is an autoimmune disease in which the disturbed dependencies between lymphocytes, dendritic cells, keratinocytes and neutrophils play the most important role. One of them is the overproduction of neutrophil extracellular traps (NETs). The release of NETs can be induced by pathogens, as well as antibodies and immune complexes, cytokines and chemokines, including TNFα. The first step of the NET creation is the activation of peptidyl arginine deiminase 4 (PAD-4). PAD-4 seems to be responsible for citrullination of histones and chromatin decondensation, but the data on PAD-4 in NETs is inconclusive. Thus, the current study aimed to determine PAD-4 and TNFα levels in the serum of psoriatic patients by ELISA and observe the response of these factors to systemic (anti-17a, anti-TNFα and methotrexate) therapies. Increased levels of both PAD-4 and its main stimulus factor TNFα in pre-treatment patients have been reported along with the concentrations of proteins correlated with disease severity (PASI, BSA). Before treatment, the irregularities in the case of anti-nuclear antibodies level (ANA) were also observed. All of the applied therapies led to a decrease in PAD-4 and TNFα levels after 12 weeks. The most significant changes, both in protein concentrations as well as in scale scores, were noted with anti-TNFα therapy (adalimumab and infliximab). This phenomenon may be associated with the inhibition of TNFα production at different stages of psoriasis development, including NET creation. The obtained data suggest the participation of PAD-4 in the activation of neutrophils to produce NETs in psoriasis, which may create opportunities for modern therapies with PAD inhibitors. However, further exploration of gene and protein expression in psoriatic skin is needed.