Allergic Fungal Rhinosinusitis (AFRS) is a chronic inflammatory condition characterized by a strong Th2 immune response. The role of genetic factors, particularly cytokine gene polymorphisms, in the development and severity of AFRS remains poorly understood. This study aimed to investigate the allelic frequencies of Th1, Th2, and Th17 cytokines in AFRS patients from the Indian population to assess their potential impact on disease outcomes. Genomic analysis revealed significant associations between specific cytokine gene polymorphisms and AFRS susceptibility. Notably, TNF-α G/A 308 polymorphism was strongly linked to the disease (p = 0.004), with the GA genotype more prevalent in AFRS patients. Additionally, IL-4-590 C/T and IL-23R gene polymorphisms exhibited distinct patterns, with the homozygous CC genotype of IL-4-590 being associated with increased AFRS susceptibility, while the T allele of IL-4 demonstrated a protective effect. The IL-13-1112 C > T polymorphism showed a higher frequency of the CC genotype in AFRS patients, suggesting a potential role in disease pathogenesis. Furthermore, the IL-17 A rs22759133 polymorphism also showed associations, with the AG genotype conferring increased risk of AFRS. These findings suggest that cytokine gene polymorphisms, particularly those affecting Th2 and Th17 pathways, may modulate immune responses and contribute to the development of AFRS. Further research with larger sample sizes is necessary to validate these findings and elucidate the genetic basis of AFRS.