Papillary thyroid cancer (PTC) is the most common type of thyroid malignancies. PTC has good prognosis, but it can dedifferentiate into aggressive forms. In this study, we aimed to identify differentially expressed genes (DEGs) between PTC samples and normal controls. We used gene expression microarrays to identify DEGs between 20 PTC samples and 10 normal controls. We performed enrichment analysis to discover biological processes and signalling pathways associated with PTC and construct protein-protein interaction (PPI) networks to find out key genes for the disease. We identified 1554 up-regulated and 912 down-regulated DEGs in PTC samples compared to normal controls. The coagulation system was the most significant pathway and SERPINA1 was the most up-regulated gene of this pathway. CCND1, PGR, CEBPA, CDKN1A, SPDEF, PLAU and MDM2 were key nodes in PPI networks. Causal network analysis revealed that SFN, which was one of the up-regulated DEGs found in our study, was the most causative upstream regulator for PTC. In conclusion, deregulation of SERPINA1, CCND1, PGR, CEBPA, CDKN1A, SPDEF, PLAU and MDM2 genes and coagulation system pathway may contribute to PTC development. SFN may be an important gene in diagnosis, prognosis and novel anticancer drug approaches for PTC. Further experiments are required to confirm the functions of identified DEGs in our study.