Discovery of cis-regulatory elements in gene promoters is a highly challenging research issue in computational molecular biology. This paper presents a novel approach to searching putative cis-regulatory elements in human promoters by first finding 8-mer sequences of high statistical significance from gene promoters of humans, mice and drosophila melanogaster respectively, and then identifying the most conserved ones across the three species (phylogenetic footprinting). In this study, a conservation analysis on both closely related species (humans and mice) and distantly related species (humans/mice and drosophila) is conducted not only to examine more candidates but also to improve the prediction accuracy. 124 putative cis-regulatory elements have been yielded and group into 20 clusters. The investigation on the coexistence of these clusters in human gene promoters reveals that SP1, EGR and NRF-1 are the dominant clusters appearing in the combinatorial combination of up to five clusters. Gene Ontology (GO) analysis also shows that many GO categories of transcription factors binding to these cis-regulatory elements match the GO categories of genes whose promoters contain these elements. In comparison with previous researches, the contribution of this study lies not only in the finding of new cis-regulatory elements, but also in its pioneering exploration on the coexistence of discovered elements and the gene ontology relationship between transcription factors and regulated genes. This exploration verifies the putative cis-regulatory elements that have been found from this study, and also gives a new insight on the regulation mechanisms of gene expression.