The neurobiological processes that underlie nicotine addiction are complex which relate to multiple factors, such as genetic and environmental factors. In this study, we applied a systems biology framework for a comprehensive functional analysis of nicotine addiction using candidate genes prioritized via a multi-source-based approach. Through integrating the information from GO, pathway and pathway crosstalk analysis, we found neurotransmitters or neurodevelopment-related signal pathway and immune system play key roles in the molecular mechanism of nicotine addiction. Further, we extracted nicotine addiction-specific subnetwork, in which some of the additional genes had been reported to be involved in nicotine addiction. To distill the global view of nicotine addiction process, we preliminarily constructed a molecular network for it. Our results provide important information for the further analysis and suggest that system level analysis is promising for understanding the pathophysiology of nicotine addiction.