Doxorubicin is a broad spectrum antitumor antibiotic. Newcastle disease virus (NDV ) is one such virus with an inherent oncolytic property. This study was done to investigate the antitumor effects of Doxorubicin and NDV on Diethylnitrosamine (DEN) induced Hepatocellular carcinoma in rats. Seventy five male albino rats were divided into five groups. Group (1): rats administered distilled water only. Group (2) : rats received diethylnitrosoamine (200 mg/kg b.wt/i.p), three times at an interval of 15 day at experimental weeks 2, 4 and 6.Group (3) : rats received DEN then treated with Doxorubicin at experimental week 10 at a dose level (2 mg/kg b.wt/i.p). Group(4): rats received DEN then treated with Hitchner B1 at experimental week 10 at a dose levels (10^7 PFU/mouse/i.p). Group(5): rats received DEN then treated with Doxorubicin at experimental week 10 at a dose level (2 mg/kg b.wt/i.p) and with Hitchner B1 at experimental week 10 at a dose levels (10^7 PFU/mouse/i.p). All animals were sacrificed after the end of experiment. DEN induced HCC showed elevation in serum ALT, AST, ALP, GGT, bilirubin. Also, resulted in upregulation in serum IL-6 and TNF- α ,On the other hand resulted in a significant decreased in serum Albumin, total protein compared with control group. Treatment with doxorubicin or/ and NDV showed that, all the parameters changed towards normal control group. The obtained results confirmed doxorubicin and NDV can inhibit the proliferation of HCC cells through improving hepatocytes.