Lymphatic metastasis is the leading cause responsible for recurrence and progression in papillary thyroid cancer (PTC), where dysregulation of lncRNAs have been extensively demonstrated to be implicated. However, the specific lymphatic node metastatsis-related (LNM) lncRNAs remain not identified in PTC yet. LNM lncRNA, MFSD4A-AS1, were explored in PTC dataset from TCGA, and our clinical samples. The roles of MFSD4A-AS1 in lymphatic metastasis were investigated by in vitro, and in vivo. Bioinformatic analysis, Luciferase assay and RIP assay were performed to identify the potential targets and the underlying pathway of MFSD4A-AS1 in lymphatic metastasis of PTC. MFSD4A-AS1 was specifically upregulated in PTC tissues with lymphatic metastasis. Upregulating MFSD4A-AS1 promoted mesh formation and migration of HUVECs and invasion and migration of PTC cells. Importantly and consistently, MFSD4A-AS1 promoted lymphatic metastasis of PTC cells in vivo by inducing the lymphangiogenic formation and enhancing invasive capability of PTC cells. Mechanistic dissection further revealed that MFSD4A-AS1 functioned as ceRNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNAs-mediated inhibition of VEGFA and VEGFC, and further activated TGF-β signaling by sponging miR-30c-2-3p that targeted TGFBR2 and USP15, both of which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC. Our results unravel a novel dual mechanisms by which MFSD4A-AS1 promotes lymphatic metastasis of PTC, which will facilitate the development of anti-lymphatic metastatic therapeutic strategy in PTC.