Hepatitis C virus (HCV) infection related hepatitis remains one of the most serious health problems worldwide. During investigation of hypervariable region 1 (HVR1) of HCV, a seven amino acids mimic peptide (GQTYTSG, named 7-P) was identified within the N-terminal of HVR1 that could protect porcine serum (PS)-induced hepatic injury in rats. 7-P could not only decrease the serum levels of aminotransferases (ALT, AST), alkaline phosphatase (AKP), and billirubin, but were also effective in reversing histopathological evidence of PS-induced rat chronic liver injury. The protective mechanism was investigated in detail using Affymetrix microarrays analysis. The bioinformatic data was confirmed by western blotting. Further studies revealed that IL-1β, tumor necrosis factor receptor superfamily 14 (TNFRSF14), intercellular adhesion molecule 2 (ICAM2), sterol regulatory element-binding protein 1 (SREBP 1), Prohibitin (PHB), and inhibitor of DNA binding 2 (Id2) were the key factors for 7-P-induced hepatoprotective effect. Together these data suggest that 7-P mimic from HVR1 of HCV protects hepatic injury by reducing the expression of key pro-inflammatory factors. 7-P might have potential therapeutic application for hepatitis in human beings.