Background Psoriasis is a prevalent disorder of primarily skin and joint affection with a well-known genetic background and a sophisticated pathogenesis. The inducible nitric oxide synthase (iNOS) gene polymorphisms are unexplored areas of research when it comes to psoriasis.Objectives The aim of the study was to investigate the probable link between iNOS gene polymorphisms (-954 G/C and Ex 16+14C/T) and susceptibility to psoriasis and psoriatic arthritis (PsA).Patients and methods We included three groups of participants: 100 participants each of psoriasis, PsA and healthy controls. Genetic polymorphism analysis was performed utilizing the PCR with the restriction fragment length polymorphism method.Results Genetic analysis of iNOS polymorphism at Ex 16+14C/T revealed significantly increased CT genotype frequency and significantly lower CC genotype frequency in psoriasis (P=0.0011, 0.003, respectively) and PsA patients (P=0.001, P<0.0001, respectively) in comparison to controls. Genetic analysis of iNOS polymorphism at −954 G/C revealed insignificant difference in genotype distribution between psoriasis patients and controls, whereas significantly increased GC genotype frequency (P=0.038) and significantly decreased GG genotype frequency (P=0.038) were detected in PsA patients versus healthy controls.Conclusions iNOS polymorphism at Ex 16+14C/T, particularly the CT genotype, is associated with psoriasis in Egyptians, whereas PsA is associated with polymorphism at Ex 16+14 and −954G/C.