Long non-coding RNAs (lncRNAs) usually refer to non-coding RNA transcripts >200 nucleotides in length. In terms of the full genomic transcript, the proportion of lncRNAs far exceeds that of coding RNA. Initially, lncRNAs were considered to be the transcriptional noise of genes, but it has since been demonstrated that lncRNAs serve an important role in the regulation of cellular activities through interaction with DNA, RNA and protein. Numerous studies have demonstrated that various intricate signaling pathways are closely related to lncRNAs. Here, we focus on a large number of studies regarding the interaction of lncRNAs with important signaling pathways. It is comprehensively illustrated that lncRNAs regulate key metabolic components and regulatory factors of signaling pathways to affect the biological activities of tumor cells. Evidence suggests that the abnormal expression or mutation of lncRNAs in human tumor cells, and their interaction with signaling pathways, may provide a basis and potential target for the diagnosis and treatment of human cancers.