BRAF mutations are frequently observed in melanoma and hairy‐cell leukemia. Currently approved rapidly accelerated fibrosarcoma (RAF) kinase inhibitors targeting oncogenic BRAF V600 mutations have shown remarkable efficacy in the clinic, but their therapeutic benefits are occasionally hampered by acquired resistance due to RAF dimerization–dependent reactivation of the downstream MAPK pathway, which is known as paradoxical activation. There is also a concern that paradoxical activation of the MAPK pathway may trigger secondary cancer progression. In this study, we developed chimeric compounds, proteolysis targeting chimeras (PROTACs), that target BRAFV600E protein for degradation. CRBN(BRAF)‐24, the most effective chimera, potently degraded BRAFV600E in a ubiquitin‐proteasome system (UPS)‐dependent manner and inhibited the proliferation of BRAFV600E‐driven cancer cells. In BRAF wild‐type cells, CRBN(BRAF)‐24 induced neither BRAFWT degradation nor paradoxical activation of the MAPK pathway. Biochemical analysis revealed that CRBN(BRAF)‐24 showed more potent and sustained suppression of MAPK signaling than a BRAFV600E inhibitor, PLX‐8394, in BRAFV600E‐driven cancer cells. Targeted degradation of BRAFV600E by CRBN(BRAF)‐24 could be a promising strategy to evade paradoxical activation of the RAF‐MAPK pathway. In this study, we developed chimeric compounds, proteolysis targeting chimeras (PROTACs), that target BRAF V600E protein for degradation. CRBN(BRAF)‐24, the most effective chimera, selectively degraded BRAF V600E in a ubiquitin‐proteasome system (UPS)‐dependent manner and inhibited the proliferation of BRAF V600E‐driven cancer cells. In BRAF wild‐type cells, CRBN(BRAF)‐24 induced neither BRAF WT degradation nor paradoxical activation of the MAPK pathway.