In this study, through naïve nanobody phage library screening, we have identified multiple nanobodies against human YAP with high affinity and specificity. The YAP nanobody was then fused to the RING domain of RNF4, creating a bio-Proteolysis-Targeting Chimera (bioPROTAC) molecule capable of selectively targeting endogenous YAP for ubiquitin-mediated degradation.