Background/Aims: Thyroid cancer accounts for about 1% of all cancer cases. Multikinase inhibitors like sunitinib (S) have a promising potential in thyroid cancer therapy. Therefore, the principal aim of this study was to investigate the impact of sunitinib on the secretion of cytokines of follicular thyroid cancer cells. Method: The effects of irradiation (R), S, and their combination (R+S) on cytokine secretion by the human thyroid cancer cell lines ML-1 and CGTH W-1 were evaluated after two (d2) and four days (d4) of treatment. Results: Multi-Analyte Profiling of cytokine release showed a decrease after S treatment (CGTH W-1: IFN-gamma, IL-4, IL-8 d2, MIP-1a, MMP-2, TNF-alpha and TNF-beta; ML-1: IFN-gamma, IL-4, IL-6, IL-7, IL-8; MIP-1 alpha, MMP-2, MCP-1, TNF-alpha and TNF-beta). R elevated significantly the release of cytokines (exception ML-1: MCP-1, MMP-2; CGTH W-1: IL-4, TNF-beta). In contrast, R+S treatment resulted in a reduction of IFN-gamma, IL-4, and MMP-2 in both cell lines. IL-6, IL-8 and MCP-1 proteins in the supernatant correlated with the data obtained by quantitative RT-PCR. VEGFD mRNAs were significantly elevated by R+S. Conclusion: A target-based therapy with R+S changed VEGFD, IL-6 and IL-8 in follicular thyroid cancer cells. These in vitro-experiments suggest IL-6, IL-8, VEGFD and TNF-alpha as interesting biomarkers to be investigated in vivo. Different reactions of the cell lines under equal treatment might be due to their different origin and characteristics. Copyright (C) 2013 S. Karger AG, Basel