During course of cancer, the cytokine profile plays a critical role in tumor fate. The multi-functional cytokines with diverse applications are involved in cancer initiation, progression and elimination. The cytokine synthesis inhibitor molecule IL10 with immune suppression and anti-angiogenic functions is considered to be prominent marker in cancer immunology. The SNPs in IL10 gene -1082 and -592 are linked with differential levels of IL-10 expression. The present case-control study deals with IL10 gene selected polymorphisms (rs180896 A/G and rs1800872 A/C) to explore their relation with breast cancer susceptibility and progression in south Indian patients. We observed a significant association of rs1800896 with BC in our study group, where AA genotype showed a two fold increased risk towards BC and three fold risk towards metastasis. In-silico analyses strengthened our observation revealing the alteration in transcription binding site in the IL10 promoter by the mutant allele G. The IL10 rs1800872 polymorphism showed an association with the susceptibility. The AA genotype showed a seven fold increased risk towards BC. The haplotype A-A was found to be two fold risk towards breast cancer (OR=1.94). The study suggests varied roles of different polymorphisms of IL10 in the aetiopathogenesis of BC. Understanding the mechanism may help in the IL10 based immunotherapy for BC treatment.