Interferon gamma (IFN-gamma) is a pro-inflammatory cytokine playing a pivotal role in both innate and adaptive immune responses. A single nucleotide polymorphism located in the first intron of the human IFN-gamma gene can influence the secretion of cytokine. Therefore, we aimed to investigate the association of IFN-gamma T/A gene polymorphism with the risk of cervical cancer. Case-control study. Uttar Pradesh State in India. Two hundred cases with histologically proven cancer of the cervix and healthy controls (n = 230), age and ethnicity matched were recruited in this study. Genotyping was performed for bi-allelic +874 (T/A) polymorphism of IFN-gamma by amplification refractory mutation system method. Low producer IFN-gamma +874 AA genotype was associated with high risk for cervical cancer, which further modulated the increased risk in tobacco users. IFN-gamma AA genotype which is low producer of IFN-gamma was associated with increased risk of cervical cancer (OR = 2.43, P = 0.003). Allele A was at 1.54-fold increased risk of cervical cancer (OR=1.54, P = 0.002). The AA genotype showed statistically significant risk with high stage (III + IV) of cervical cancer (OR = 4.99, P = 0.001). In tobacco users, AA genotype showed significantly increased susceptibility to cervical cancer (OR = 5.08, P = 0.010). Variation in IFN-gamma +874 AA genotype because of ethnicity in north-Indian population may represent an important susceptibility biomarker for cervical cancer risk as well as other diseases and should be explored further.