Long non-coding RNAs (lncRNAs) play biological roles through a variety of mechanisms, including genetic imprinting, chromatin remodeling, cell cycle control, splicing regulation, mRNA decay, and translational regulation. LncRNAs are involved in the regulation of gene expression through the above mechanisms in different levels. Establishment and application of research technologies are important in understanding of lncRNAs functions. Microarray, RNA sequencing, Northern blot, real time quantitative reverse transcription-polymerase chain reaction, fluorescence in situ hybridization, RNA interference, and RNA-binding protein immunoprecipitation are major tools of exploring biological functions of lncRNAs. Here, we highlighted three advanced methods, i.e., fast predictions of RNA and protein interactions and domains (catRAPID), chromatin isolation by RNA purification (ChIRP), and combined knockdown and localization analysis of non-coding RNAs (c-KLAN).