The relationship between the chemistry characteristic and the hepatoprotective effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione (DDD), a curcumin analogue, in operative liver injury rats was investigated to reveal the mechanism of hepatic protection effects of DDD. DDD (1.2–4.8 mmol/kg) was administrated 10 min before reperfusion phase in hepatic ischemia-reperfusion injury (IRI) rats. DDD (4.8 mmol/kg) administrated 10 min before ischemia and N-acetylcysteine (NAC) (4.8 mmol/kg) administrated 10 min before reperfusion were included for comparative studies. The plasma liver enzyme activities, histopathological indices and markers of lipid peroxide were determined to evaluate the hepatic protection effects. Effects of DDD on succinate dehydrogenase (SDH) activity were also investigated. DDD showed dose-dependent hepatocyte protections when administrated 10 min before reperfusion stages in hepatic IRI rats. DDD showed almost equivalent hepatoprotective effects when administrated 10 min before ischemia phase demonstrating that DDD acted on the reperfusion stages selectively against the hepatic IRI, instead of ischemia phase. NAC was not effective against hepatic IRI when treated 10 min before reperfusion because of the higher pKa of NAC. In additional, DDD had no effect on the SDH both in hepatic IRI rats and in mitochondria. In conclusion, DDD had dose-dependent hepatocyte protections in the reperfusion stages in hepatic IRI rats, while the observed hepatocyte protections of DDD did not involve SDH activities. β-Diketone structures of DDD were crucial for the hepatocyte protections. The abilities of DDD to clear up the unsaturated aldehydes related with the enolate nucleophilicity and the pKa. DDD might be a promising candidate to treat hepatic IRI.