IL-6/STAT3 signaling pathway has been suggested to play a role in CTCL pathogenesis. Polymorphisms in STAT3 signaling pathway-related genes might be a risk factor for CTCL. However, the exact role of inherited gene polymorphisms of IL-6 and STAT3 in the pathogenesis of CTCL is still not fully understood. The aim was to examine whether IL-6 cytokine and polymorphisms of IL-6 and STAT3 gene are associated with CTCL susceptibility, stage of disease and pruritus intensity. We compared the IL-6 serum level and the frequency of selected single nucleotide polymorphisms of IL-6 and STAT3 in 106 CTCL and 198 control group using polymerase chain reaction with sequence-specific primers method and ELISA. We have found that serum IL-6 level in CTCL patients was significantly higher than in healthy controls (p < 0.05). We also demonstrated that two genotypes, CC of IL-6 and GG of STAT3, were overexpressed in CTCL patients compared to healthy controls, and that they increase the risk of malignancy development (OR = 1.8, p = 0.04 for IL-6 and OR 2.53, p = 0.0064 for STAT3). Moreover, the GG genotype of STAT3 polymorphism seems to be associated with lack of pruritus or mild pruritus in CTCL patients. Our results indicate that IL-6 is involved in pathogenesis of CTCL but not pruritus. Moreover, CC of IL-6 and GG genotype of STAT3 genes might be considered as the risk factor for development of CTCL.