Apoptosis is essential for cellular homeostasis and normal development. Aberrant apoptosis (too much or too less) is associated with many important diseases such as autoimmune diseases and cancer. Studies have led to the identification of a number of proteins and microRNAs involved in the regulation of apoptosis. However, the role of long non-coding RNAs (lncRNAs) is still unclear. In this study, two cancer therapeutics drugs, cisplatin and doxorubicin, and two ligands, Fas mAb and TNF-alpha, were used in identification of differentially expressed pathway-drug specific and/or global lncRNAs in apoptotic HeLa cells. Following dose-kinetics experiments the level of apoptosis was measured by Flow Cytometry and was further verified by Fluorescence Microscopy and Western Blotting via measurement of Caspase 3, 8 and 9 protein levels. Three replicates of total RNAs (control and drug/ligand-treated cells) were sent to deepsequencing using the Illumina platform. The resulting reads matched to the human genome greater than 95%. Under our experimental setting, treatments with cisplatin, doxorubicin, Fas mAb and TNF-alpha led to the differential expression of 1644, 506, 584 and 807 lncRNAs, respectively (2-fold or higher, P < 0.01). Two of identified lncRNAs common for all inducers was in antisense position to TRAIL-R2 receptor and FasR associated factor which play directly in apoptosis. Results suggest that many lncRNAs are differentially expressed upon treatment with the indicated agents. Functional characterization of candidates might provide an interesting insight into regulation of apoptosis. Keywords: apoptosis, long non-coding RNA, deep sequencing