Introduction: 10-30% of patients with Papillary thyroid cancer (PTC) recur and may become de-differentiated. Interaction between Programmed cell death protein(PD-1) and its ligand(PD-L1) has been found to have an important role in oncogenesis. This study aims to identify the association of these checkpoint inhibitors with clinicopathological variables in PTC. Methodology: 29 patients who underwent total thyroidectomy for PTC between April 2016 to March 2017 were included. PD-1 and PD-L1 immunohistochemistry were done on the surgical specimens. Results: PD-L1 expression in the tumor was seen in 62%, of which it was strongly positive in 21%. PD-1 expression was negative in all specimens. In tumor-infiltrating lymphocytes (TILs), PD-L1 hotspots were seen in 24% with 17.2% being in the range of 26-40%. 62% of the samples with a classical variant of PTC were either moderately/ strongly positive for PD-L1 expression and 30.8% had positive PD-1 TIL hotspots (p<0.05). Hobnail, cribriform morular, and tall cell variants were negative for PD-L1 expression and PD-1 hotspots in TIL (p<0.05). PD-L1 expression was seen in 60% of the cases with extrathyroidal extension (ETE) and all cases with lymphovascular invasion and perinodal extension (p<0.05). No association was found between the strength of PD-L1 expression and ETE. 80% of cases with ETE were negative for PD-1 hotspots in TILs. The percentage of PD-1 TIL hotspots did not correlate with any of these clinical parameters. Conclusion: PD-1 and PD-L1 expression are associated with aggressive PTC behavior and can serve as a prognostic marker for personalized therapeutic strategies.