Objective: Tumor microenvironment (TME) is complex, with crosstalk between cancer cells and other cells contributing to cancer development. FGD5-AS1 is an oncogenic long noncoding ribonucleic acid (lncRNA) derived from exosome in cancer cells. It was shown that cancer cells can regulate macrophage polarization to a state favorable to cancer development. The aim of this study was to explore the role of exosome-derived FGD5-AS1 in the interaction between thyroid cancer (TC) cells and macrophages, and provide new insights into the mechanisms underlying TC development. Methods: Macrophage M2 polarization in the collected clinical TC cell tissues was observed through flow cytometry. To examine the effect of TC cells on macrophage polarization, macrophages were co-incubated with SW1736 cells and then exosome secretion inhibitor (GW4869) was added. To observe the role of FGD5-AS1 in SW1736-derived exosomes, SW1736 cells were transfected with FGD5-AS1 overexpression vector, and SW1736-derived exosomes (SW1736FGD5-AS1-Exos) were later isolated, followed by a treatment of macrophages. The number of macrophages expressing cluster of differentiation 163 (CD163) under different treatment was detected with flow cytometry, and the expression of Arginase 1 (Arg-1), cluster of differentiation 206 (CD206), interleukin 10 (IL-10) and FGD5-AS1 was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). After DiO labeling of exosomes (SW1736-Exos), the endocytosis of exosomes in macrophages were observed. In order to explore the effect of macrophages on SW1736 cells, the medium of macrophages treated by different exosomes was incubated with SW1736 cells. Finally, the migration and invasion of SW1736 cells were observed by scratch assay and Transwell. Results: TC cell tissues appeared to be infiltrated by significantly larger number of M2 macrophages, compared with para-cancerous tissues (p < 0.05). When macrophages were co-incubated with SW1736 cells, a significant increase in macrophage M2 polarization was observed, but the increase was significantly inhibited by GW4869. SW1736-Exos could be endocytosed by macrophages and significantly promote macrophage M2 polarization, while SW1736FGD5-AS1-Exos was able to significantly enhance the promotion (p < 0.05). Macrophages treated with SW1736FGD5-AS1-Exos significantly increased the migration and invasion ability of SW1736 cells (p < 0.05). Conclusions: FGD5-AS1 carried by TC cell-derived exosomes induces macrophage M2 polarization, while M2 macrophages promote migration and invasion of TC cells.