Besides DSB repair proteins, mutations in long non-coding RNAs (lncRNAs) are associated with tumorigenesis. Large scale screening has provided novel p53 interactors, including lncRNAs, which can be potential therapeutic targets [41–43]. Researchers have identified 22 distinct lncRNAs that are involved in the regulation of chemoresistance in cancers . How the lncRNA regulatory networks act in concert to modulate oncogenesis and therapeutic response remains largely unknown. Here we review the most recent findings on lncRNAs with well-characterized functions in DDR.