A huge amount of microarray datasets are produced with big number of genes and small samples. Feature selection methods have become a very sharp tool to select the gene signatures from the whole gene set. In recent years, researchers are concerned much about the datasets containing samples of cancer as well as corresponding control tissues. However, few feature selection methods consider the effect of paired samples. In this article, we propose a new feature selection method for paired microarray datasets based on the original paired t-test approach. We apply on the paired datasets across six common cancer types. Through comparison with some widely used methods on the performance of prediction power, stability of gene lists and functional stability, our method shows excellent performance. The proposed method has good effectiveness, stability and consistency, which enables the method to be applicative to feature selection for paired microarray expression data analysis.