The efficient treatment of the disease such as non-alcoholic fatty liver disease as a global concern is impeded by the limited understanding of the disease complexity. We applied a systems-biology framework for a functional analysis of disease development using candidate genes. We identified, the keys dysregulation, pathways, and Hub-genes leading the disease. Moreover, we constructed a molecular disease network for the disease via integrating the pathways, providing an intuitional view to understand the development. In addition, the druggability of genes and their new application in terms of marker discovery or new drug discovery were examined. Our analyses identify a series of highly overexpressed genes, also featuring high centrality, yet being less underlined in the context of NAFLD development in the previous research. We also found several relatively low overexpressed genes, having a central place in the PPI network topology, whose potential involvement in non-alcoholic steatohepatitis might be undermined otherwise using network biology. Our results reveal that the biological processes related to disease progression are complex. Indeed, our pathway studies identified Hub genes, which may reinforce poly-pharmacological cross-talks followed by disease progression to irreversible stages holistic approaches via systems biology tools help us identify more reliable targets and disease-mediated genes integrated into translational studies and drug development in this area.