Long non-coding RNAs (lncRNAs) are a group of endogenous RNA molecules which exceed 200 nt in length, lack complete specific open reading frame, and completely lack or possessvery limited protein-coding capacity. Recent studies have revealed that lncRNAs participate in critical processes such as genomic imprinting, cell differentiation, and immune reaction, etc. lncRNAs regulate gene expression at the epigenetic, transcriptional and post-transcriptional levels by modulating chromatin remodeling and histone modifications, interfering the transcription, regulating patterns of alternative splicing, generating small RNAs, and modulating protein activation and localization. Through their numerous functions, lncRNAs play critical roles in the growth, development, senescence, death, and other important physiological and pathological processes. Further investigation into the regulation of gene expression mediated by lncRNAs will be of great value in the thorough understanding of pathogenies and provide new molecular markers and drug targets of diseases.