Atezolizumab plus bevacizumab is the recommended first-line treatment for unresectable hepatocellular carcinoma, based on guidelines from the Barcelona Clinic Liver Cancer prognosis and treatment strategy. However, atezolizumab plus bevacizumab may be used after administration of lenvatinib. Here, we present four patients who developed thyroid dysfunction after second-line treatment with atezolizumab plus bevacizumab, but not after lenvatinib alone. The patients were treated with lenvatinib and/or atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma at Showa University Northern Yokohama Hospital. Of patients treated with only lenvatinib or atezolizumab plus bevacizumab, 2/18 (11%) and 4/15 (27%) developed thyroid dysfunction, respectively. All four patients treated with atezolizumab plus bevacizumab after lenvatinib developed hypothyroidism after 2-14 doses of atezolizumab plus bevacizumab. Three patients developed Grade 2 symptoms and were treated with levothyroxine sodium. In patients with hepatocellular carcinoma, the incidence of thyroid dysfunction may be higher among patients treated with atezolizumab plus bevacizumab after lenvatinib than those treated with lenvatinib or atezolizumab plus bevacizumab alone.