Long noncoding RNAs (lncRNAs) are widely known for their regulatory function in transcriptional and posttranscriptional processes. The involvement of such non-protein-coding RNAs in nuclear organization and chromatin remodeling is often associated with an increased risk of human malignancies. In cancer, lncRNAs either promote cell survival or may act as a growth suppressor, thus conferring a key regulatory function other than their established role in fundamental cellular processes. Interestingly, lncRNAs interfere with the stages of apoptosis and related pathways involving p53. Many of these molecules either regulate or are regulated by p53 while mounting oncogenic events. Consequently, they may confer both prosurvival or proapoptotic functions depending upon the tissue type. Since the mechanism of cell death is bypassed in many human cancers, it has emerged that the lncRNAs are either overexpressed or knocked down to sensitize cells to apoptotic stimuli. Nonetheless, the abundant expression of lncRNAs in tumor cells renders them suitable targets for anticancer therapies. Although the role of lncRNAs in the p53 network and apoptosis has been independently defined, their interplay in activating p53-target genes during cell cycle arrest remains unexplored. Thus, we have specifically reviewed the possible involvement of lncRNAs in the p53-mediated apoptosis of human cancer cells. In particular, we summarize the growing evidence from individual studies and analyze whether lncRNAs are essential to facilitate apoptosis in a p53-dependent manner. This may lead to the identification of p53-associated lncRNAs that are suitable therapeutic targets or diagnostic/prognostic markers. © 2021 International Federation for Cell Biology