Background Psoriasis is a chronic dermatologic disease affecting 2% of the general population. Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a newly defined member of the TNF family. Increased serum levels of TWEAK were reported in inflammatory diseases. The relationship between serum TWEAK levels and severity of psoriasis has not yet been proven. Our aim was to clarify the change in serum TWEAK levels in response to conventional and anti-TNF treatments. Material and methods Blood samples were collected from 103 moderate or severe chronic plaque psoriasis patients with or without arthritis who were referred to the Department of Dermatology, Istanbul University Cerrahpasa Medical Faculty between the years 2016 and 2018. Psoriasis Area and Severity Index (PASI) scores were calculated, and serum TWEAK levels were assessed with TWEAK ELISA kit. SPSS 20 was used for statistics. Results Serum TWEAK levels increased significantly and PASI scores decreased significantly after both conventional and anti-TNF treatments, but the two variables were not correlated. There was no significant difference between conventional and anti-TNF treatments, between patients with or without comorbid arthritis and between genders. Conclusions Lower serum TWEAK levels induce psoriasis and higher levels of TWEAK are observed after treatment. It is important to determine a threshold value. Such a cutoff value of serum TWEAK levels could not be calculated in our study similar to previous studies. If its serum levels were to be standardized in further studies, TWEAK can be used as a follow-up marker in psoriasis patients with the PASI score.