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Background: Sunitinib, commonly used for metastatic renal cell carcinoma (mRCC), often induces hypothyroidism, affecting 27 to 85% of patients. There are clues suggesting an association between sunitinib-induced hypothyroidism and improved survival outcomes. This study aims to identify the predictive factors of sunitinib-induced hypothyroidism and evaluate whether the occurrence of overt or subclinical hypothyroidism predicts tumor outcome in patients with mRCC. Methods: Patients administered to sunitinib for mRCC was included in this retrospective study. Log-rank test and Cox proportional hazards model were conducted to identify predictive factors of hypothyroidism and prognostic factors of progression-free survival (PFS) and overall survival (OS). Results: A total of 156 patients with mRCC treated with sunitinib were included. Predictive factors of sunitinib-induced hypothyroidism were female (odds ratio (OR), 2.77), sunitinib-induced hypertension (OR, 2.99) and dose reduction of sunitinib due to intolerance (OR, 3.57). Sunitinib-induced overt hypothyroidism was a significant prognostic factor in predicting PFS and OS (hazard ratio, 0.38 and 0.23, respectively). Thyroid hormone replacement did not have an influence on PFS and OS. Conclusions: Female patients, patients who experienced sunitinib-induced hypertension and sunitinib dose reduction are at higher risk of hypothyroidism and need close monitoring. Overt hypothyroidism is a strong prognostic factor of sunitinib treatment outcome in mRCC patients and thyroid hormone replacement does not have a negative effect on tumor outcome.