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Abstract Hepatocellular carcinoma (HCC) represents a complex and fatal malignant disease driven primarily by oxidative stress and inflammation. Due to poor prognosis and limited therapeutic interventions, chemoprevention has emerged as a viable approach to reduce the morbidityand mortality of HCC. The aim of the present study was to investigate the possible protective and therapeutic effects of cranberry extract (CE) and celery seed oil (CO) against diethylnitrosamine(DENA)-induced hepatocellular carcinoma in rats in addition to their effects on cisplatin(Cis)-anticancer and toxic actions. Average liver weight, serum liver enzymes, serum alpha-fetoprotein (AFP), hepatocyte paraffin-1 (hep-Par1) expression and liver histopathological examination were selected to evaluate the protective and therapeutic effects of the different regimens. In an attempt to understand the mechanisms involved in the anticancer effect, hepatic oxidative stress biomarkers namely lipid peroxides, reduced glutathione and catalase were measured, the expression of proliferating cell nuclear antigen (PCNA) and apoptotic marker caspase-3 were investigated, the pro-inflammatory mediators namely serum TNF-Ü, liver nitric oxide content, cyclooxygenase-2 (COX-2) and nuclear factor-kappaB (NF-mB) were also studied in the liver to verify the role of protein expression in liver treatment and protection. Treatment of HCC rats with CE (200 mg/kg) or CO (300 mg/kg) decreased the liver index, attenuated the rise of the aminotransferases (ALT and AST), alkaline phosphatase, gamma glutamyl transferase and total bilirubin, decreased the serum level of the tumour marker AFP and hepPar-1 hepatic expression parallel to improvement in the histopathological findings. Amelioration of oxidative stress was verified by a decrease in liver lipid peroxides level along with increased GSH content and catalase activity |