Background: The miRNAs, a class of short approximately 22-nucleotide non-coding RNAs, often act post-transcriptionally to inhibit mRNA expression. In effect, they control gene expression by targeting mRNA. They also help in carrying out normal functioning of a cell as they play an important role in various cellular processes. However, dysregulation of miRNAs is found to be a major cause of a disease. It has been demonstrated that miRNA expression is altered in many human cancers, suggesting that they may play an important role as disease biomarkers. Multiple reports have also noted the utility of miRNAs for the diagnosis of cancer. Among the large number of miRNAs present in a microarray data, a modest number might be sufficient to classify human cancers. Hence, the identification of differentially expressed miRNAs is an important problem particularly for the data sets with large number of miRNAs and small number of samples.Results: In this regard, a new miRNA selection algorithm, called μHEM, is presented based on rough hypercuboid approach. It selects a set of miRNAs from a microarray data by maximizing both relevance and significance of the selected miRNAs. The degree of dependency of sample categories on miRNAs is defined, based on the concept of hypercuboid equivalence partition matrix, to measure both relevance and significance of miRNAs. The effectiveness of the new approach is demonstrated on six publicly available miRNA expression data sets using support vector machine. The.632+ bootstrap error estimate is used to minimize the variability and biasedness of the derived results.Conclusions: An important finding is that the μHEM algorithm achieves lowest B.632+ error rate of support vector machine with a reduced set of differentially expressed miRNAs on four expression data sets compare to some existing machine learning and statistical methods, while for other two data sets, the error rate of the μHEM algorithm is comparable with the existing techniques. The results on several microarray data sets demonstrate that the proposed method can bring a remarkable improvement on miRNA selection problem. The method is a potentially useful tool for exploration of miRNA expression data and identification of differentially expressed miRNAs worth further investigation. © 2013 Paul and Maji; licensee BioMed Central Ltd.