The underlying pathophysiological mechanisms involved in cerebral aneurysms rupture remain unclear. This study was performed to investigate the differentially expressed proteins between ruptured and unruptured aneurysms using quantitative proteomics. The aneurysmal walls of six ruptured aneurysms and six unruptured aneurysms were collected during the surgical operation. The isobaric tags for relative and absolute quantification (iTRAQ) were used to identify the differentially expressed proteins and western blotting was performed to validate the expression of the proteins of interest. Bioinformatics analysis of the differentially expressed proteins was also performed using the KEGG database and GO database. Between ruptured and unruptured aneurysms, 169 proteins were found differently expressed, including 74 up-regulated proteins and 95 down-regulated proteins with a fold change >= 2 and p value <= .05. KEGG pathway analysis revealed that phagosome, focal adhesion and ECM-receptor interaction were the most common pathways involved in aneurysm rupture. In addition, the differential expressions of ITGB3, CRABP1 and S100A9 were validated by western blotting. Through the iTRAQ method, we found that inflammatory responses and cell-matrix interactions may play a significant role in the rupture of cerebral aneurysms. These findings provide a basis for better understanding of pathophysiological mechanisms associated with aneurysm rupture.