With the development of sequencing technology, a large number of long non-coding RNAs (lncRNAs) have been identified in addition to coding genes. LncRNAs, originally considered as junk RNA, are dysregulated in various types of cancer. Although protein-coding signaling pathways underlie various biological activities, and abnormal signal transduction is a key trigger and indicator for tumorigenesis and cancer progression, lncRNAs are sparking keen interest due to their versatile roles in fine-tuning signaling pathways. We are just beginning to scratch the surface of lncRNAs. Therefore, despite the fact that lncRNAs drive malignant phenotypes from multiple perspectives, in this review, we focus on important signaling pathways modulated by lncRNAs in cancer to demonstrate an up-to-date understanding of this emerging field.