There is a growing interest for epigenetics in recent years. The main patterns of epigenetic regulation include DNA methylation, histone modification and chromatin remodeling, etc. The outcome of ENCODE project and subsequent studies have revealed that only a small portion of human genome encodes proteins, while the vast majority are transcribed as non-coding RNA (ncRNA). Long non-coding RNA (lncRNA) is commonly defined as an RNA molecule which is larger than 200 nucleotides (nt) and not translated into proteins. Growing evidences have suggested that lncRNAs can regulate gene expression at various levels including epigenetic regulation, transcriptional regulation and post-transcriptional regulation, and are involved in a wide variety of biological processes, such as cell proliferation, differentiation and apoptosis. In this review, we highlight the recent advances of how lncRNAs function in the epigenetic regulation.