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<strong>Background and objectives:</strong> Non-alcoholic fatty liver disease (NAFLD) is a common liver condition. On the other hand, coffee consumption has shown promising for gastrointestinal diseases.  Detection of the most valuable biomarkers of decaffeinated coffee treatment in healthy and non-alcoholic fatty liver disease conditions was the aim of the present study. <strong>Methods:</strong> A previous proteomics study about effect of decaffeinated coffee (1.5 mL daily drinking coffee for two months) on protein expression change of rat liver was selected for protein-protein interaction (PPI) network analysis via Cytoscape v.3.7.1 and the related applications. The most central proteins with regards to a high degree and betweenness centralities in the coffee treatment condition of healthy and NAFLD were then analyzed by ClueGO for biological process (BP) derivation. <strong>Results: </strong>HSPA5, HSPA4, HSPA9, HSPA7, PARK7, HSP90AA1, P4HB, PRDX1, and PDIA3 were introduced as central proteins, which are involved in folding and antioxidant activities. <strong>Conclusion:  </strong>There is a complicated combination of the components in coffee; some elements are involved in liver protection against NAFLD and the others are in contrast.