The purpose of the present study was to evaluate the preventive effects of hydrazinocurcumin (HZC) ondiethylnitrosamine (DEN)-induced hepatocarcinogenesis in a male Sprague Dawley (SD) rat model. One hundredand twenty male SD rats used in this study were divided into six groups. Those receiving DEN with curcumin(CUR) or HZC were studied compared with the DEN-alone group. The study demonstrated that DEN inducedsevere histological and immunohistochemical changes in liver tissues, significantly increasing the levels of livermarker enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase(ALP), γ-glutamyltransferase (GGT) and total bilirubin level (TBL)). The hepatocarcinoma incidenceswere 100.0%, 36.7% and 20.0% in the DEN-alone, DEN-CUR and DEN-HZC groups, respectively. Althoughmacroscopic and microscopic features suggested that both CUR and HZC were effective in inhibiting DENinducedhepatocarcinogenesis, HZC was exerted a stronger influence. Immunohistochemical analysis with PCNAdemonstrated significantly differences among the groups (all P < 0.05). Taken together, the results suggestedapplication of CUR and HZC could prevent the occurrence of carcinogenesis and HZC may be a more potentcompound for prevention of DEN-induced hepatocarcinogenesis in rats than CUR.