Introduction: Accounting for 80-85% of all thyroid cancers, papillary thyroid cancer (PTC) is a common endocrine malignancy and is categorized into numerous types of variant, such as follicular-variant PTC (FVPTC) and common conventional PTC (CPTC), as well as some unusual variants. BRAF mutations in thyroid cancer cause treatment resistance and MAPK signaling. Considering the oncogenic role of BRAF mutation in this disease, emphasis has been made on BRAF kinase inhibition to be improved in PTC treatment.Methods: In this study, we searched PubMed database to find English articles related to our topic applying the keywords of Papillary thyroid cancer (PTC), BRAF mutations, BRAF/MEK inhibitors, drug resistance, vemurafenib and treatment.Results: A proper treatment for radioiodine-refractory differentiated thyroid carcinoma can be redifferentiation therapy with BRAF/MEK inhibitors used for facilitation of radioiodine treatment. However, the current preliminary clinical results were meek. BRAF/MEK inhibitors-induced activation of HER2/HER3 causes MAPK rebound, which is a mechanism of resistance and its integration with HER inhibitor might sensitize BRAFV600E in order to inhibit MAPK rebound. In order to be used for patients with PTC harboring the BRAFV600E mutation, vemurafenib must be evaluated more to find its favorable impacts. As such, an indirect anti-tumor effect can be allowed by BRAF inhibition owing to its direct anti-tumor impact or restore radioiodine uptake. Uptake of radioactive iodine in patients with metastatic BRAFV600E-positive iodine-refractory PTC is stimulated by the BRAF-specific inhibition inhibition of dabrafenib.Conclusion: Drug resistance in redifferentiation treatments might be adequately explained by feedback mechanism that restricts the impacts of RAF/MEK inhibitors on downstream signaling in PTC. It is suggested that future studies be conducted to more efficiently comprehend clinical consequences in a long period, safety of chronic medical therapy in this population of patients, and mechanisms of tumor resistance to selective BRAF kinase inhibition.