Polo‐like kinases (PLKs) are potent regulators of cell proliferation and cell survival. Polo‐like kinases are potential targets in the treatment of anaplastic thyroid cancer (ATC), a rare but deadly disease. The therapeutic effects of volasertib, a PLK inhibitor, was evaluated for the treatment of ATC either alone or in combination with sorafenib. Volasertib decreased cell viability in three ATC cell lines (8505C, 8305C, and KAT18) in a dose‐dependent manner. Volasertib caused ATC cells to accumulate in G2/M phase, activated caspase‐3 activity, and induced apoptosis. Combination therapy using volasertib and sorafenib in ATC cells showed mostly synergistic effects. In vivo studies revealed that combination therapy of volasertib and sorafenib was effective in the treatment of 8505C xenografts. Single‐agent volasertib treatment was sufficient to retard 8305C tumor growth. No substantial morbidity was observed in animals that received either single‐agent or combination treatment. These preclinical findings suggest that volasertib could be an effective drug in treating ATC. Anaplastic thyroid cancer is a rare but deadly disease. Polo‐like kinases (PLKs) are potent regulators of cell proliferation and cell survival. We found that PLK inhibitor volasertib, either alone and in combination with sorafenib, was effective in the treatment of anaplastic thyroid cancer in vitro and in vivo.