Cell proliferation is the crucial process for many physiological incidents such as tissue and organ development, wound healing, and immune system reactions. It is achieved by the growth and division of cells in a multicellular organism. Investigation of molecules involved in the regulation of cell cycle mechanism provides insight into reasons and treatments of the diseases such as cancer. In recent years, information that acquired from deep sequencing reveals that several proteins and non-coding RNAs have crucial role in the regulation of cell cycle and proliferation. Death receptor 5 antisense (DR5-AS) is a novel long non-coding RNA (lncRNA) transcript that is cisplatin inducible and is involved in modulation of cell proliferation and cell cycle in HeLa cells. When DR5-AS lncRNA was knocked down, the morphology of HeLa cells became spherical without inducing apoptosis. Although this lncRNA reduces cell proliferation via a cell cycle arrest at S and G2/M phases, mechanism behind this cell cycle arrest is not known. lncRNAs work in complexes with RNA, DNA, and protein interactions in the cell. There are several experimental and bioinformatical approaches to investigate RNA: protein interactions such as PAR-CLIP. In this approach, proximal protein and RNAs are covalently bonded with UV radiation. Then this complex is immunoprecipitated with specific antibodies. According to PAR-CLIP data of DR5-AS lncRNA, CAPRIN1 is a cell cycle associated protein that has the highest interaction score. The results suggest that CAPRIN1 and DR5-AS work reversely in cell proliferation although under the cisplatin treatment, CAPRIN1 enhances the expression of DR5-AS lncRNA. All these observations were confirmed by many quantitative experiments. Conclusively, this study provides a clue about how DR5-AS lncRNA might regulate cell cycle and proliferation through CAPRIN1 protein.