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Brain metastasis in differentiated thyroid cancer (DTC) is rare (frequency < 1%) and has a poor prognosis. Treatment strategies for brain metastasis are not well established.We conducted a retrospective analysis to identify predictive factors for patient outcomes and verify surgical indications for patients with brain metastasis and DTC.The study included 34 patients with pathologically confirmed DTC with brain metastasis from March 2008 to November 2020. The associations between overall survival (OS) and clinical factors were evaluated. Cox regression analysis was used to determine the relationship between clinical factors and OS. To assess the survival benefit of craniotomy, Kaplan–Meier survival analysis was performed for each variable whose statistical significance was determined by Cox regression analysis.The median OS of the entire patient sample was 11.4 months. Survival was affected by the presence of lung metastasis (P= 0.033) and the number of brain metastases (n  > 3) (P= 0.039). Only the subgroup with the number of brain metastases ≤3 showed statistical significance in the subgroup analysis of survival benefit following craniotomy (P= 0.048).The number of brain metastases and the existence of lung metastasis were regarded more essential than other clinical factors in patients with DTC in this study. Furthermore, craniotomies indicated a survival benefit only when the number of brain metastases was ≤3. This finding could be beneficial in determining surgical indications in thyroid cancer with brain metastasis.