Abstract: MicroRNAs are small non-coding RNAs, which regulate the protein encoding genes at post-transcriptional level. Topological and dynamic features of protein-protein interaction network provide insights of biological processes. We have performed topological analysis to elucidate the global correlation between microRNA regulation and protein interaction network in human. The results showed that microRNA targets tend to be hubs and bottlenecks in the network. While proteins directly regulated by microRNA might not form a network module themselves, the microRNA targets and their interacting proteins jointly show significantly higher network density and modularity. With gene expression profiles in different biological states, we further examined the dynamic structure of microRNA-regulated networks, and developed a network-based method to identify active microRNAs and reveal their functional roles in specific biological condition. Applying the analysis to gastric cancer, we found a key microRNA that plays an important role in tumor suppression and elaborated its regulatory mechanism in cancer cells.