Oesophageal carcinoma is one of the most lethal cancer types in the world, especially in some part of China. Oesophageal squamous cell carcinoma (OSCC) is a major subtype, which has been shown to be associated with unhealthy diet habit, smoking, environmental carcinogens etc. The OSCC often progress slowly, however, it is often diagnosed at an advanced stage. Thus it is imperative to elucidate the molecular mechanisms involved in the initiation and progression of OSCC. Long noncoding RNAs (lncRNA) has emerged as a novel functional player transcribed from the genome. Here, we describe a novel lncRNA POU6F2-AS2 specifically expressed in OSCC. POU6F2-AS2 is involved in the DNA damage response and regulates cells survival after ionizing radiation. POU6F2-AS2 interacts with Ybx1 protein and regulates its chromatin localization. Our current study represents the first description of an OSCC associated lncRNA that modulates DNA repair.