Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency diseases. Cytokine production could be affected in CVID patients, whereas its alteration could be due to genetic polymorphisms within coding and promoter regions of the cytokine genes. This study was performed to analyse the proinflammatory cytokine single nucleotide polymorphisms in CVID. The allele and genotype frequencies of a number polymorphic genes coding tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-1R, IL-1RA and IL-6 were investigated and compared between two groups of CVID patients and controls. The IL-6 GA genotype at position nt565 was significantly over-represented in the patient group (P<0.001), while the IL-6 GG genotype at position -174 (P=0.006) and the GG genotype at position nt565 (P<0.001) were significantly lower than controls. The TNF-alpha AG genotype at position -308 in the patient group was increased significantly in comparison with controls (P=0.027), but the GG genotype at the same position was significantly decreased (P=0.011). IL-6 CA and GA haplotypes were the most frequent haplotypes in the patients (P<0.005), whereas TNF-alpha GA (P=0.002) and IL-6 GG (P<0.001) haplotypes were decreased significantly in the patients in comparison with controls. Cytokine single nucleotide polymorphisms could have a role in pathophysiology of CVID. High production of TNF-alpha is expected in some CVID patients based on the frequency of genotypes/haplotypes of these cytokine gene polymorphisms.