The analysis of gene expression is able to identify many possible transcription factor regulated gene groups. It has been proven that the phylogenetic footprinting method can help to identify transcription factor binding sites. Our work develops an expert system that combines motif searching and phylogenetic footprinting. After a motif and a gene group are submitted, the expert system is able to evaluate the statistics of the motifs appearance across all genes in genome and in gene upstream conserved regions by comparing human and mouse. A transcription factor-target gene group was used to test the proposed system. The results show that the system is able to distinguish transcription factor-target gene groups from random gene groups. By comparing motif distribution between all genes and a gene group, the proposed system is able to help biologists identify possible transcription factor regulated gene groups that have co-regulated gene expression (C) 2008 Elsevier Ltd. All rights reserved.