AbstractLong non-coding RNAs (lncRNAs) have been demonstrated to play essential roles in diverse cellular processes and biological functions. Exploring the functions associated with lncRNAs may help provide insight into their underlying biological mechanisms. The current methods primarily focus on investigating the functions of individual lncRNAs; however, essential biological functions may be affected by the combinatorial effects of multiple lncRNAs. Here, we have developed a novel computational method, LncRNAs2Pathways, to identify the functional pathways influenced by the combinatorial effects of a set of lncRNAs of interest based on a global network propagation algorithm. A new Kolmogorov–Smirnov-like statistical measure weighted by the network propagation score, which considers the expression correlation among lncRNAs and coding genes, was used to evaluate the biological pathways influenced by the lncRNAs of interest. We have described the LncRNAs2Pathways methodology and illustrated its effectiveness by analyzing three lncRNA sets associated with glioma, prostate and pancreatic cancers. We further analyzed the reproducibility and robustness and compared our results with those of two other methods. Based on these analyses, we showed that LncRNAs2Pathways can effectively identify the functional pathways associated with lncRNA sets. Finally, we implemented this method as a freely available R-based tool.