Analyzing omics data from a network-based perspective can facilitate biomarker discovery. To improve disease diagnosis and identify prospective information indicating the onset of complex disease, a computational method for identifying potential biomarkers based on differential sub-networks (PB-DSN) is developed. In PB-DSN, Pearson correlation coefficient (PCC) is used to measure the relationship between feature ratios and to infer potential networks. A differential sub-network is extracted to identify crucial information for discriminating different groups and indicating the emergence of complex diseases. Subsequently, PB-DSN defines potential biomarkers based on the topological analysis of these differential sub-networks. In this study, PB-DSN is applied to handle a static genomics dataset of small, round blue cell tumors and a time-series metabolomics dataset of hepatocellular carcinoma. PB-DSN is compared with support vector machine-recursive feature elimination, multivariate empirical Bayes statistics, analyzing time-series data based on dynamic networks, molecular networks based on PCC, PinnacleZ, graph-based iterative group analysis, KeyPathwayMiner and BioNet. The better performance of PB-DSN not only demonstrates its effectiveness for the identification of discriminative features that facilitate disease classification, but also shows its potential for the identification of warning signals.