Introduction: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Apart from genetics, autoimmunity has been implicated in its pathogenesis. In this context, we set out to study the role of Pro- inflammatory cytokines in PTC in South Indian population.rnMaterial and methods: This pilot prospective case-control study was conducted on surgically managed PTC patients. Institutional ethical committee approval was obtained. Diagnosis of PTC was based on imaging, fine needle aspiration cytology and later confirmed by histopathology. Exclusion criteria were subjects with any disease or medication interfering with the hypothalamic-pituitary-gonadal axis. Serum samples were collected from 46 PTC subjects and 44 age matched healthy controls. Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α) and high sensitive C reactive protein (hsCRP), leptin levels were measured in all serum samples. Statistical analysis was performed by one way ANOVA with Dunnet’s test and Pearson correlation tests.rnResults: The mean hSCRP level in PTC and controls were 18.3 ± 3.1 mg/mL and 5.5 ± 1.2 mg/mL respectively. The mean TNF-α level, IL-6 level and Leptin levels were 295 ± 28 pg/mL, 13.6 ± 4.4 pg/mL and 1.93 ± 0.8 ng/mL respectively. Serum leptin level in controls was 3.6 ±1.8 ng/mL. There was statistically significant difference of all the pro-inflammatory cytokines compared to controls (P value <0.05) with negative correlation for leptin levels. rnConclusions: Our study shows raised titers of pro-inflammatory markers – IL-6, TNF-α and hsCRP, while reduced leptin levels correlated with PTC suggesting a contributory role. But, the exact immuno-modulatory mechanism needs more research.