In the last few years, accumulating evidences had demonstrated that long non-coding RNAs (lncRNAs) participated in the regulation of target gene expression and played an important role in biological processes and human disease development. Thus, prediction of the associations between lncRNAs and disease had become a hot research in the fields of human sophisticated diseases. Most of these methods considered the information of two networks (lncRNA, disease) while neglected other networks. In this study, we designed a multi-layer network by integrating the similarity networks of lncRNAs, diseases and genes, and the known association networks of lncRNA-disease, lncRNAs-gene, and disease-gene, and then we developed a model called MHRWR for predicting the lncRNA-disease potential associations based on random walk with restart. The performance of MHRWR was evaluated by experimentally verified lncRNA-disease associations based on leave-one-out cross validation. MHRWR obtained a reliable AUC value of 0.91344, which significantly outperformed some previous methods. To further validate the reproducibility of performance, we used the model of MHRWR to verify related lncRNAs of colon cancer, colorectal cancer and lung adenocarcinoma in the case studies. The codes of MHRWR is available on: https://github.com/yangyq505/MHRWR.