Long noncoding RNA (lncRNA), a subgroup of noncoding RNA with > 200 nt, plays critical roles in cancer progression. Here, we aimed to explore the detailed biological function of lncRNA EGFEM1P during papillary thyroid cancer (PTC) progression. RT-qPCR and Western blot were used to analyze the expression of lncRNA EGFEM1P, miR-6867-5p, and CHI3L1. CCK8, colony formation, and Transwell migration assays were undertaken to assess PTC cell proliferation and migration. A xenograft tumor mouse model was also used to establish tumor growth in vivo. Luciferase reporter and anti-AGO2 RNA immunoprecipitation (RIP) assays were used to clarify the interplay between miR-6867-5p and lncRNA EGFEM1P or CHI3L1. We found lncRNA EGFEM1P and CHI3L1 to be highly expressed in PTC tissues and cells, while miR-6867-5p expression decreases. Functionally, lncRNA EGFEM1P silence delays PTC cell proliferation and migration, and impairs tumorigenesis in vivo. LncRNA EGFEM1P targets miR-6867-5p, and CHI3L1 is a target gene of miR-6867-5p. LncRNA EGFEM1P silence decreases the pro-proliferation and pro-migration caused by the miR-6867-5p inhibitor in PTC cells, and CHI3L1 silence abrogates the pro-tumorigenic action resulting from the miR-6867-5p inhibitor in PTC cells. Our data showed that lncRNA EGFEM1P targeting of the miR-6867-5p/CHI3L1 axis drives PTC progression, suggesting lncRNA EGFEM1P as a therapeutically
target for PTC.