Analyzing topological properties of drug-target proteins in the biology network is very helpful in understanding the mechanism of drug action. However, comprehensive studies to elaborately characterize the biological network features of drug-target proteins are still lacking. In this paper, we compared the topological properties of drug–targets with those of the non–drug-target sets, by mapping the drug–targets in DrugBank to the human protein interaction network. The results indicate that the topological properties of drug-targets are significantly distinguishable from those of non–drug-targets. Moreover, the potential possibility of drug-target prediction based on these properties is discussed. All proteins in the interaction network were ranked by their topological properties. Among the top 200 proteins, 94 overlapped with drug-targets in DrugBank and some novel predictions were found to be drug–targets in public literatures and other databases. In conclusion, our method explores the topological properties of drug-targets in the human protein interaction network by exploiting the large–scale drug-targets and protein interaction data.