Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides in length that, in general, do not appear to have protein-coding potential. lncRNAs act in gene regulation involved with several biological processes. Furthermore, lncRNAs have been associated with a significant number of cancers, suggesting a potential role in tumorigenesis and progression. For example, HOTAIR regulates proliferation processes and other lncRNAs like highly upregulated in liver cancer (HULC), H19, PTENP1, HEIH, and antisense noncoding RNA in the INK4 locus (ANRIL). Other lncRNAs as AFAP1-AS1 and lincRNA-p21 can interact with BCL-2 and TP53, acting in apoptosis. Moreover, NORAD plays a vital role in genomic stability. Additionally, due to deregulated expression and high tissue specificity level, lncRNAs exhibit great potential as prognostic markers. In this chapter, we review the most highlighted lncRNAs acting in hallmarks of cancer and clinical application.