TAR DNA‐binding protein 43 (TDP‐43) is an RNA‐binding protein, whose loss‐of‐function mutation causes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Recent studies demonstrated that TDP‐43 binds to the 3′ untranslated region (UTR) of target mRNAs to promote mRNA instability. Here, we show that TDP‐43 recruits Caf1 deadenylase to mRNA targets and accelerates their deadenylation. Tethering TDP‐43 to the mRNA 3′UTR recapitulates destabilization of the mRNA, and TDP‐43 accelerates their deadenylation. This accelerated deadenylation is inhibited by a dominant negative mutant of Caf1. We find that TDP‐43 physically interacts with Caf1. In addition, we provide evidence that TDP‐43 regulates poly(A) tail length of endogenous Progranulin (GRN) mRNA. These results may shed light on the link between dysregulation of TDP‐43‐mediated mRNA deadenylation and pathogenesis of neurodegenerative diseases.