The aim of this study was to investigate the tumor suppressive effects of saffron in an experimental hepatocellular carcinoma (HCC) model in rats. Thirty rats were included in this study and divided into:- Control group : Rats which receive distilled water only. HCC group : induced by diethylnitrosamine (DEN) and CCl4 only. Saffron group : Rats were administered orally saffron respectively 2 weeks prior to HCC initiation and continued for 6 weeks. The effect of saffron on ALT and AST activity and albumin level were studied also TGF-beta level and the TAC level were estimated and induction of apoptosis was determined by histopathological studies. Treatment with saffron was significantly decreased the activities of ALT and AST also increased the albumin level, decreased the TGF-beta level and increased the TAC level, it also reduced the elevation in the number and the incidence of hepatic dyschromatic nodules. Moreover, treatment with saffron extract brought significant restoration of the hematological parameters to values that were comparable to those of the negative control group, it also enhances the liver and kidney health, this study provides evidence that saffron exerts anti-oxidant, chemoperventive effect against liver cancer through induction of apoptosis as appeared in histopathological studies