Gene regulatory networks have an important role in every process of life, including cell differentiation, metabolism, the cell cycle and signal transduction. The RASSF1A is a tumor suppressor gene involved in several growth regulatory and pro-apoptotic pathways. In this study, we have used microarray technology to define differences in the gene expression profiles subsequent to exogenous wild-type RASSF1A in melanoma A375 cells. Gene expression changes were verified in a subset of genes using real time RT-PCR. Association of modulated genes with biological functional groups identified several pathways affected by RASSF1A including cell death, cellular growth and proliferation, and cellular development. GRN of modulated genes were identified using the STRING. Pro-inflammatory factors and transcription factors locates in the center of RASSF1A modulated gene regulatory networks. Our results suggested that RASSF1A might affect melanoma gene regulatory network via modulating the expression and interaction between pro-inflammatory factors and transcription factors.