Long non-coding RNAs (lncRNAs) transcribed extensively from the genome have been proposed to be key regulators of diverse biological processes. However, little is known about the role of lncRNAs in regulation of the cell-cycle G1/S checkpoint following DNA damage, a key step in the maintenance of genomic fidelity. Here we show that growth-arrested DNA damage-inducible gene 7 (gadd7), a DNA damage-inducible lncRNA, regulates the G1/S checkpoint in response to UV irradiation. Interestingly, UV-induced gadd7 directly binds to TAR DNA-binding protein (TDP-43) and interferes with the interaction between TDP-43 and cyclin-dependent kinase 6 (Cdk6) mRNA, resulting in Cdk6 mRNA degradation. These findings demonstrate a role for gadd7 in controlling cell-cycle progression and define a novel mechanism by which lncRNAs modulate mRNA expression at the post-transcriptional level by altering mRNA stability.