Recent studies exploring the underlying pathomechanisms of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder, have focused on biomolecular condensates, such as stress granules (SGs) and TDP-43 condensates. Our comprehension of the physicochemical processes that control the behavior of these condensates is still evolving. In this work, we reveal an unexpected function for YAP, a central component of the Hippo pathway, in regulating the dynamic behavior of SGs and TDP-43 condensates, a role that is independent of its transcriptional activity in Hippo pathway. We found that YAP can directly bind to the TB domain of TDP-43 through its N-terminal domain. This interaction promotes the homotypic multimerization and phase separation of TDP-43, while inhibiting its hyper- phosphorylation and solidification under stress conditions. Remarkably, YAP, whose mRNA level is reduced in ALS patients, is found to co-localize with pathological pTDP-43 aggregates in the cytoplasmic foci of ALS patient brains. Additionally, elevating YAP/Yorkie expression substantially reduces neurotoxicity in a TDP-43 transgenic fly model of ALS. Our findings highlight an unexpected chaperone-like role of YAP in managing ALS-associated biomolecular condensates, presenting significant implications for potential ALS treatments.