Long noncoding RNAs (lncRNAs) are a class of non-protein coding transcripts exceeding 200 nucleotides in length. Accumulating evidence achieved by several sophisticated techniques such as chromatin conformation capture and RNA-seq has led to new questions concerning correlations between lncRNAs and chromatin structures. Many studies have revealed that lncRNAs exert great influences on gene expression through regulating chromatin 3D structures. In addition, lncRNAs play a crucial role in tumorigenesis and therefore hold great promises in disease diagnosis and prognosis. Here, we mainly focus on introducing how lncRNAs regulate gene expression by modulating nuclear architecture and discussing clinical values of lncRNAs in oncotherapy.